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Sample records for model nascent hdl

  1. Understanding HDL function : studies in preclinical models and patients

    NARCIS (Netherlands)

    Annema, Wijtske

    2013-01-01

    HDL-functie draagt mogelijk bij aan het risico op hart- en vaatziekten Slecht werkende High-density lipoproteïne (HDL) draagt mogelijk bij aan het risico op hart- en vaatziekten. Dat concludeert Wijtske Annema, die onderzoek deed naar de relatie tussen HDL-functie en hart- en vaatziekten. HDL wordt

  2. Understanding HDL function : studies in preclinical models and patients

    NARCIS (Netherlands)

    Annema, Wijtske

    2013-01-01

    HDL-functie draagt mogelijk bij aan het risico op hart- en vaatziekten Slecht werkende High-density lipoproteïne (HDL) draagt mogelijk bij aan het risico op hart- en vaatziekten. Dat concludeert Wijtske Annema, die onderzoek deed naar de relatie tussen HDL-functie en hart- en vaatziekten. HDL wordt

  3. Stochastic Kinetics of Nascent RNA

    Science.gov (United States)

    Xu, Heng; Skinner, Samuel O.; Sokac, Anna Marie; Golding, Ido

    2016-09-01

    The stochastic kinetics of transcription is typically inferred from the distribution of RNA numbers in individual cells. However, cellular RNA reflects additional processes downstream of transcription, hampering this analysis. In contrast, nascent (actively transcribed) RNA closely reflects the kinetics of transcription. We present a theoretical model for the stochastic kinetics of nascent RNA, which we solve to obtain the probability distribution of nascent RNA per gene. The model allows us to evaluate the kinetic parameters of transcription from single-cell measurements of nascent RNA. The model also predicts surprising discontinuities in the distribution of nascent RNA, a feature which we verify experimentally.

  4. High-Alfa Aerodynamics with Separated Flow Modeled as a Single Nascent Vortex

    Science.gov (United States)

    Antony, Samuel B.; Mukherjee, Rinku

    2017-04-01

    A numerical iterative vortex lattice method is developed to study flow past wing(s) at high angles of attack where the separated flow is modelled using NY nascent vortex filaments. The wing itself is modelled using NX × NY bound vortex rings, where NX and NY are the number of sections along the chord and span of the wing respectively. The strength and position of the nascent vortex along the chord corresponding to the local effective angle of attack are evaluated from the residuals in viscous and potential flow, i.e. (Cl)visc - (Cl)pot and (Cm)visc - (Cm)pot. Hence, the 2D airfoil viscous Cl - α and Cm - α is required as input (from experiment, numerical analysis or CFD). Aerodynamic characteristics and section distribution along span are predicted for 3D wings at a high angle of attack. Effect of initial conditions and existence of multiple solutions in the post-stall region is studied. Results are validated with experiment.

  5. Genetic disorders of HDL metabolism: from model to mechanism

    NARCIS (Netherlands)

    Holleboom, A.G.

    2011-01-01

    Mensen met een hoog HDL-cholesterol in het bloed lopen minder kans op hart- en vaatziekten. Onno Holleboom ontdekte twee enzymen, LCAT en ppGaINAc-T2, die een belangrijke rol spelen in het HDL-metabolisme. Zij vormen daardoor potentiële aangrijpingspunten voor toekomstige therapieën.

  6. In Vivo PET Imaging of HDL in Multiple Atherosclerosis Models

    DEFF Research Database (Denmark)

    Pérez-Medina, Carlos; Binderup, Tina; Lobatto, Mark E

    2016-01-01

    OBJECTIVES: The goal of this study was to develop and validate a noninvasive imaging tool to visualize the in vivo behavior of high-density lipoprotein (HDL) by using positron emission tomography (PET), with an emphasis on its plaque-targeting abilities. BACKGROUND: HDL is a natural nanoparticle......,2-distearoyl-sn-glycero-3-phosphoethanolamine-deferoxamine B). Biodistribution and plaque targeting of radiolabeled HDL were studied in established murine, rabbit, and porcine atherosclerosis models by using PET combined with computed tomography (PET/CT) imaging or PET combined with magnetic resonance imaging......-injection for both (89)Zr-HDL nanoparticles. In the porcine model, increased accumulation of radioactivity was observed in lesions by using in vivo PET imaging. Irrespective of the radiolabel's location, HDL nanoparticles were able to preferentially target plaque macrophages and monocytes. CONCLUSIONS: (89)Zr...

  7. Identification of Nascent Memory CD8 T Cells and Modeling of Their Ontogeny.

    Science.gov (United States)

    Crauste, Fabien; Mafille, Julien; Boucinha, Lilia; Djebali, Sophia; Gandrillon, Olivier; Marvel, Jacqueline; Arpin, Christophe

    2017-03-22

    Primary immune responses generate short-term effectors and long-term protective memory cells. The delineation of the genealogy linking naive, effector, and memory cells has been complicated by the lack of phenotypes discriminating effector from memory differentiation stages. Using transcriptomics and phenotypic analyses, we identify Bcl2 and Mki67 as a marker combination that enables the tracking of nascent memory cells within the effector phase. We then use a formal approach based on mathematical models describing the dynamics of population size evolution to test potential progeny links and demonstrate that most cells follow a linear naive→early effector→late effector→memory pathway. Moreover, our mathematical model allows long-term prediction of memory cell numbers from a few early experimental measurements. Our work thus provides a phenotypic means to identify effector and memory cells, as well as a mathematical framework to investigate their genealogy and to predict the outcome of immunization regimens in terms of memory cell numbers generated. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  8. HDL genes & HDL drugs

    NARCIS (Netherlands)

    Vergeer, A.M.H.

    2011-01-01

    Menno Vergeer onderzocht de genetische basis van het menselijk HDL-cholesterolmetabolisme door middel van familieonderzoek en genetische associatiestudies in grote cohorten. Mutaties in verschillende cholesterolvervoerders zijn van invloed op de productie van insuline in de alvleesklier en van stero

  9. HDL genes & HDL drugs

    NARCIS (Netherlands)

    Vergeer, A.M.H.

    2011-01-01

    Menno Vergeer onderzocht de genetische basis van het menselijk HDL-cholesterolmetabolisme door middel van familieonderzoek en genetische associatiestudies in grote cohorten. Mutaties in verschillende cholesterolvervoerders zijn van invloed op de productie van insuline in de alvleesklier en van

  10. VERHOG HDL MODELING%硬件描述语言Verilog的建模技术

    Institute of Scientific and Technical Information of China (English)

    蒋敬旗; 胡燕翔; 刘明业

    2001-01-01

    Through analyzing the hierarchical modeling, gate - level modeling, clataflow modeling, behavioral modeling andswitch-level modeling, this paper expounds the modeling method of Verilog HDL. It is useful to study and use the Verilog HDL,and it is also meaningful to constitute the language standard of Verilog HDL in Ghina%通过对Verilog语言的层次化建模、门级建模、数据流级建模、行为建模、开关级建模等各个抽象层次的研究,全面阐述了Verilog的建模方法。对于理解、使用和制订我国的Verilog语言标准会有所帮助。

  11. The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model.

    Directory of Open Access Journals (Sweden)

    Wenrui Hao

    Full Text Available Atherosclerosis, the leading death in the United State, is a disease in which a plaque builds up inside the arteries. As the plaque continues to grow, the shear force of the blood flow through the decreasing cross section of the lumen increases. This force may eventually cause rupture of the plaque, resulting in the formation of thrombus, and possibly heart attack. It has long been recognized that the formation of a plaque relates to the cholesterol concentration in the blood. For example, individuals with LDL above 190 mg/dL and HDL below 40 mg/dL are at high risk, while individuals with LDL below 100 mg/dL and HDL above 50 mg/dL are at no risk. In this paper, we developed a mathematical model of the formation of a plaque, which includes the following key variables: LDL and HDL, free radicals and oxidized LDL, MMP and TIMP, cytockines: MCP-1, IFN-γ, IL-12 and PDGF, and cells: macrophages, foam cells, T cells and smooth muscle cells. The model is given by a system of partial differential equations with in evolving plaque. Simulations of the model show how the combination of the concentrations of LDL and HDL in the blood determine whether a plaque will grow or disappear. More precisely, we create a map, showing the risk of plaque development for any pair of values (LDL,HDL.

  12. The LDL-HDL profile determines the risk of atherosclerosis: a mathematical model.

    Science.gov (United States)

    Hao, Wenrui; Friedman, Avner

    2014-01-01

    Atherosclerosis, the leading death in the United State, is a disease in which a plaque builds up inside the arteries. As the plaque continues to grow, the shear force of the blood flow through the decreasing cross section of the lumen increases. This force may eventually cause rupture of the plaque, resulting in the formation of thrombus, and possibly heart attack. It has long been recognized that the formation of a plaque relates to the cholesterol concentration in the blood. For example, individuals with LDL above 190 mg/dL and HDL below 40 mg/dL are at high risk, while individuals with LDL below 100 mg/dL and HDL above 50 mg/dL are at no risk. In this paper, we developed a mathematical model of the formation of a plaque, which includes the following key variables: LDL and HDL, free radicals and oxidized LDL, MMP and TIMP, cytockines: MCP-1, IFN-γ, IL-12 and PDGF, and cells: macrophages, foam cells, T cells and smooth muscle cells. The model is given by a system of partial differential equations with in evolving plaque. Simulations of the model show how the combination of the concentrations of LDL and HDL in the blood determine whether a plaque will grow or disappear. More precisely, we create a map, showing the risk of plaque development for any pair of values (LDL,HDL).

  13. A model for the origin of protein synthesis as coreplicational scanning of nascent RNA.

    Science.gov (United States)

    Yakhnin, Alexander V

    2007-12-01

    The origin of protein synthesis is one of the major riddles of molecular biology. It was proposed a decade ago that the ribosomal RNA evolved from an earlier RNA-replisome (a ribozyme fulfilling RNA replication) while transfer RNA (tRNA) evolved from a genomic replication origin. Applying these hypotheses, I suggest that protein synthesis arose for the purpose of segregating copy and template RNA during replication through the conventional formation of a complementary strand. Nascent RNA was scanned in 5' to 3' direction following the progress of replication. The base pairing of several tRNA-like molecules with nascent RNA released the replication intermediates trapped in duplex. Synthesis of random peptides evolved to fuel the turnover of tRNAs. Then the combination of replication-coupled peptide formation and the independent development of amino acid-specific tRNA aminoacylation resulted in template-based protein synthesis. Therefore, the positioning of tRNAs adjacent to each other developed for the purpose of replication rather than peptide synthesis. This hypothesis does not include either selection for useful peptides or specific recognition of amino acids at the initial evolution of translation. It does, however, explain a number of features of modern translation apparatus, such as the relative flexibility of genetic code, the number of proteins shared by the transcription and translation machines, the universal participation of an RNA subunit in co-translational protein secretion, 'unscheduled translation', and factor-independent translocation. Assistance of original ribosomes in keeping apart the nascent transcript from its template is still widely explored by modern bacteria and perhaps by other domains of life.

  14. Verification and Diagnosis Infrastructure of SoC HDL-model

    CERN Document Server

    Hahanov, Vladimir; Litvinova, Eugenia; Chumachenko, Svetlana

    2012-01-01

    This article describes technology for diagnosing SoC HDL-models, based on transactional graph. Diagnosis method is focused to considerable decrease the time of fault detection and memory for storage of diagnosis matrix by means of forming ternary relations in the form of test, monitor, and functional component. The following problems are solved: creation of digital system model in the form of transaction graph and multi-tree of fault detection tables, as well as ternary matrices for activating functional components in tests, relative to the selected set of monitors; development of a method for analyzing the activation matrix to detect the faults with given depth and synthesizing logic functions for subsequent embedded hardware fault diagnosing.

  15. Explaining nascent entrepreneurship across countries

    NARCIS (Netherlands)

    A.R. Thurik (Roy); A.J. van Stel (André); A.R.M. Wennekers (Sander); P. Reynolds (Paul)

    2003-01-01

    textabstractThis paper aims at explaining cross-country variation in nascent entrepreneurship. Regression analysis is applied using various explanatory variables derived from three different approaches. We make use of the Global Entrepreneurship Monitor database, including nascent entrepreneurship r

  16. Explaining nascent entrepreneurship across countries

    NARCIS (Netherlands)

    A.R. Thurik (Roy); A.J. van Stel (André); A.R.M. Wennekers (Sander); P. Reynolds (Paul)

    2003-01-01

    textabstractThis paper aims at explaining cross-country variation in nascent entrepreneurship. Regression analysis is applied using various explanatory variables derived from three different approaches. We make use of the Global Entrepreneurship Monitor database, including nascent entrepreneurship r

  17. Explaining nascent entrepreneurship across countries

    NARCIS (Netherlands)

    A.R. Thurik (Roy); A.J. van Stel (André); A.R.M. Wennekers (Sander); P. Reynolds (Paul)

    2003-01-01

    textabstractThis paper aims at explaining cross-country variation in nascent entrepreneurship. Regression analysis is applied using various explanatory variables derived from three different approaches. We make use of the Global Entrepreneurship Monitor database, including nascent entrepreneurship

  18. Explaining variation in nascent entrepreneurship

    NARCIS (Netherlands)

    A.J. van Stel (André); A.R.M. Wennekers (Sander); P. Reynolds (Paul); A.R. Thurik (Roy)

    2004-01-01

    textabstractThis paper aims at explaining cross-country variation in nascent entrepreneurship. Regression analysis is applied using various explanatory variables derived from three different approaches. We make use of the Global Entrepreneurship Monitor database, including nascent entrepreneurship r

  19. Role of apolipoprotein A-II in the structure and remodeling of human high-density lipoprotein (HDL): protein conformational ensemble on HDL.

    Science.gov (United States)

    Gao, Xuan; Yuan, Shujun; Jayaraman, Shobini; Gursky, Olga

    2012-06-12

    High-density lipoproteins (HDL, or "good cholesterol") are heterogeneous nanoparticles that remove excess cell cholesterol and protect against atherosclerosis. The cardioprotective action of HDL and its major protein, apolipoprotein A-I (apoA-I), is well-established, yet the function of the second major protein, apolipoprotein A-II (apoA-II), is less clear. In this review, we postulate an ensemble of apolipoprotein conformations on various HDL. This ensemble is based on the crystal structure of Δ(185-243)apoA-I determined by Mei and Atkinson combined with the "double-hairpin" conformation of apoA-II(dimer) proposed in the cross-linking studies by Silva's team, and is supported by the wide array of low-resolution structural, biophysical, and biochemical data obtained by many teams over decades. The proposed conformational ensemble helps integrate and improve several existing HDL models, including the "buckle-belt" conformation of apoA-I on the midsize disks and the "trefoil/tetrafoil" arrangement on spherical HDL. This ensemble prompts us to hypothesize that endogenous apoA-II (i) helps confer lipid surface curvature during conversion of nascent discoidal HDL(A-I) and HDL(A-II) containing either apoA-I or apoA-II to mature spherical HDL(A-I/A-II) containing both proteins, and (ii) hinders remodeling of HDL(A-I/A-II) by hindering the expansion of the apoA-I conformation. Also, we report that, although endogenous apoA-II circulates mainly on the midsize spherical HDL(A-I/A-II), exogenous apoA-II can bind to HDL of any size, thereby slightly increasing this size and stabilizing the HDL assembly. This suggests distinctly different effects of the endogenous and exogenous apoA-II on HDL. Taken together, the existing results and models prompt us to postulate a new structural and functional role of apoA-II on human HDL.

  20. HDL functionality in reverse cholesterol transport--Challenges in translating data emerging from mouse models to human disease.

    Science.gov (United States)

    Lee-Rueckert, Miriam; Escola-Gil, Joan Carles; Kovanen, Petri T

    2016-07-01

    Whereas LDL-derived cholesterol accumulates in atherosclerotic lesions, HDL particles are thought to facilitate removal of cholesterol from the lesions back to the liver thereby promoting its fecal excretion from the body. Because generation of cholesterol-loaded macrophages is inherent to atherogenesis, studies on the mechanisms stimulating the release of cholesterol from these cells and its ultimate excretion into feces are crucial to learn how to prevent lesion development or even induce lesion regression. Modulation of this key anti-atherogenic pathway, known as the macrophage-specific reverse cholesterol transport, has been extensively studied in several mouse models with the ultimate aim of applying the emerging knowledge to humans. The present review provides a detailed comparison and critical analysis of the various steps of reverse cholesterol transport in mouse and man. We attempt to translate this in vivo complex scenario into practical concepts, which could serve as valuable tools when developing novel HDL-targeted therapies.

  1. HDL Cholesterol Test

    Science.gov (United States)

    ... products and services. Advertising & Sponsorship: Policy | Opportunities HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  2. HDL and the menopause.

    Science.gov (United States)

    El Khoudary, Samar R

    2017-08-01

    To summarize recent provocative findings on conventional and novel metrics of HDL including HDL-C, HDL subclasses and HDL cholesterol efflux capacity as related to menopause. Pattern of menopause-related changes in HDL-C are not consistent, suggesting a complex relationship between HDL and menopause. Growing body of literature indicates that higher levels of HDL-C may not be consistently cardio-protective in midlife women, suggesting a potential change in other metrics of HDL that could not be captured by the static metric HDL-C. It is also possible that higher HDL-C at certain conditions could be a marker of HDL metabolism dysfunctionality. Significant alterations in other metrics of HDL have been reported after menopause and found to be related to estradiol. The impact of changes in novel metrics of HDL over the menopausal transition on cardiovascular disease (CVD) risk later in life is not clear in women. Much of our understanding of how the menopausal transition may impact HDL metrics comes from cross-sectional studies. Future longitudinal studies are needed to evaluate other metrics of HDL shown to better reflect the cardio-protective capacities of HDL, so that the complex association of menopause, HDL and CVD risk could be characterized.

  3. HDL endocytosis and resecretion.

    Science.gov (United States)

    Röhrl, Clemens; Stangl, Herbert

    2013-11-01

    HDL removes excess cholesterol from peripheral tissues and delivers it to the liver and steroidogenic tissues via selective lipid uptake without catabolism of the HDL particle itself. In addition, endocytosis of HDL holo-particles has been debated for nearly 40years. However, neither the connection between HDL endocytosis and selective lipid uptake, nor the physiological relevance of HDL uptake has been delineated clearly. This review will focus on HDL endocytosis and resecretion and its relation to cholesterol transfer. We will discuss the role of HDL endocytosis in maintaining cholesterol homeostasis in tissues and cell types involved in atherosclerosis, focusing on liver, macrophages and endothelium. We will critically summarize the current knowledge on the receptors mediating HDL endocytosis including SR-BI, F1-ATPase and CD36 and on intracellular HDL transport routes. Dependent on the tissue, HDL is either resecreted (retro-endocytosis) or degraded after endocytosis. Finally, findings on HDL transcytosis across the endothelial barrier will be summarized. We suggest that HDL endocytosis and resecretion is a rather redundant pathway under physiologic conditions. In case of disturbed lipid metabolism, however, HDL retro-endocytosis represents an alternative pathway that enables tissues to maintain cellular cholesterol homeostasis.

  4. HDL endocytosis and resecretion☆

    Science.gov (United States)

    Röhrl, Clemens; Stangl, Herbert

    2013-01-01

    HDL removes excess cholesterol from peripheral tissues and delivers it to the liver and steroidogenic tissues via selective lipid uptake without catabolism of the HDL particle itself. In addition, endocytosis of HDL holo-particles has been debated for nearly 40 years. However, neither the connection between HDL endocytosis and selective lipid uptake, nor the physiological relevance of HDL uptake has been delineated clearly. This review will focus on HDL endocytosis and resecretion and its relation to cholesterol transfer. We will discuss the role of HDL endocytosis in maintaining cholesterol homeostasis in tissues and cell types involved in atherosclerosis, focusing on liver, macrophages and endothelium. We will critically summarize the current knowledge on the receptors mediating HDL endocytosis including SR-BI, F1-ATPase and CD36 and on intracellular HDL transport routes. Dependent on the tissue, HDL is either resecreted (retro-endocytosis) or degraded after endocytosis. Finally, findings on HDL transcytosis across the endothelial barrier will be summarized. We suggest that HDL endocytosis and resecretion is a rather redundant pathway under physiologic conditions. In case of disturbed lipid metabolism, however, HDL retro-endocytosis represents an alternative pathway that enables tissues to maintain cellular cholesterol homeostasis. PMID:23939397

  5. EFEK PEMBERIAN SUSU SAPI BUBUK TERHADAP KADAR SERUM HDL (HIGH DENSITY LIPOPROTEIN PADA TIKUS PUTIH (Rattus norvegicus GALUR WISTAR MODEL DIABETES MELITUS TIPE 2

    Directory of Open Access Journals (Sweden)

    Zakia Umami

    2015-05-01

    Full Text Available ABSTRACTThe purpose of this study was to determine the cow’s milk powder to increased serum levels of High Density Lipoprotein (HDL of white male rat model with diabetes mellitus type 2. The design of this study was a post-test control group study conducted in 30 male rats which randomly divided into five groups. Negative control group was the group of rats which fed normally, the positive control group was induced by streptozotocin (STZ without given cow’s milk, group P1, P2, P3 were given a normal diet and cow’s milk 0.9; 1.8, and 2.7 g orally every day. The results of this study were the levels of HDL in K(-=44.22 mg/dl, K(+=47.45 mg/dl, P1=56.56 mg/dl, P2=51.82 mg/dl, and P3=59.45 mg/dl. The conclusion was the milk powder was not significantly increase levels of HDL (p>0.05. More longer intervention was suggested for further research to get more significant of HDL level on type 2 diabetes mellitus.Keywords: HDL serum level, high fat diet, milk powder, streptozotocinABSTRAKTujuan penelitian ini adalah menganalisis pengaruh pemberian susu sapi bubuk terhadap peningkatan kadar serum High Density Lipoprotein (HDL tikus putih (Rattus norvegicus berjenis kelamin jantan model diabetes melitus (DM tipe 2. Penelitian ini menggunakan desain penelitian post test control group dengan 30 ekor tikus dibagi secara acak menjadi lima kelompok. Kelompok K(- adalah tikus yang diberi pakan normal, kelompok K(+ diinduksi dengan streptozotocin (STZ tanpa diberi susu, kelompok P1 sampai P3 diberi diet normal dan susu 0,9; 1,8, dan 2,7 g secara oral setiap hari. Hasil penelitian menunjukkan kadar HDL pada K(-=44,22 mg/dl, K(+=47,45 mg/dl, P1=56,56 mg/dl, P2=51,82 mg/dl, dan P3=59,45 mg/dl. Susu sapi bubuk mampu meningkatkan kadar HDL tikus model DM tipe 2 akan tetapi tidak signifikan (p>0,05. Perlu dilakukan penelitian lebih lanjut dengan waktu lama penelitian yang berbeda sehingga bisa berdampak yang lebih signifikan untuk kadar HDL pada DM tipe 2.Kata kunci

  6. From nascent to actual entrepreneurship: the effect of entry barriers

    OpenAIRE

    Stel, André; Storey, David; Wennekers, Sander; Thurik, Roy

    2006-01-01

    textabstractThis exploratory study focuses on the conversion from nascent to actual entrepreneurship and the role of entry barriers in this process. Using data for a sample of countries participating in the Global Entrepreneurship Monitor between 2002 and 2004, we estimate a twoequation model explaining the nascent entrepreneurship rate and the young business entrepreneurship rate, while taking into account the interrelationship between the two variables (i.e. the conversion). Furthermore var...

  7. Effects of Dietary Flavonoids on Reverse Cholesterol Transport, HDL Metabolism, and HDL Function.

    Science.gov (United States)

    Millar, Courtney L; Duclos, Quinn; Blesso, Christopher N

    2017-03-01

    Strong experimental evidence confirms that HDL directly alleviates atherosclerosis. HDL particles display diverse atheroprotective functions in reverse cholesterol transport (RCT), antioxidant, anti-inflammatory, and antiapoptotic processes. In certain inflammatory disease states, however, HDL particles may become dysfunctional and proatherogenic. Flavonoids show the potential to improve HDL function through their well-documented effects on cellular antioxidant status and inflammation. The aim of this review is to summarize the basic science and clinical research examining the effects of dietary flavonoids on RCT and HDL function. Based on preclinical studies that used cell culture and rodent models, it appears that many flavonoids (e.g., anthocyanidins, flavonols, and flavone subclasses) influence RCT and HDL function beyond simple HDL cholesterol concentration by regulating cellular cholesterol efflux from macrophages and hepatic paraoxonase 1 expression and activity. In clinical studies, dietary anthocyanin intake is associated with beneficial changes in serum biomarkers related to HDL function in a variety of human populations (e.g., in those who are hyperlipidemic, hypertensive, or diabetic), including increased HDL cholesterol concentration, as well as HDL antioxidant and cholesterol efflux capacities. However, clinical research on HDL functionality is lacking for some flavonoid subclasses (e.g., flavanols, flavones, flavanones, and isoflavones). Although there has been a tremendous effort to develop HDL-targeted drug therapies, more research is warranted on how the intake of foods or specific nutrients affects HDL function. © 2017 American Society for Nutrition.

  8. HDL efflux capacity, HDL particle size, and high-risk carotid atherosclerosis in a cohort of asymptomatic older adults: the Chicago Healthy Aging Study.

    Science.gov (United States)

    Mutharasan, R Kannan; Thaxton, C Shad; Berry, Jarett; Daviglus, Martha L; Yuan, Chun; Sun, Jie; Ayers, Colby; Lloyd-Jones, Donald M; Wilkins, John T

    2017-03-01

    HDL efflux capacity and HDL particle size are associated with atherosclerotic CVD (ASCVD) events in middle-aged individuals; however, it is unclear whether these associations are present in older adults. We sampled 402 Chicago Healthy Aging Study participants who underwent a dedicated carotid MRI assessment for lipid-rich necrotic core (LRNC) plaque. We measured HDL particle size, HDL particle number, and LDL particle number with NMR spectroscopy, as well as HDL efflux capacity. We quantified the associations between HDL particle size and HDL efflux using adjusted linear regression models. We quantified associations between the presence of LRNC and HDL and LDL particle number, HDL particle size, and HDL efflux capacity using adjusted logistic regression models. HDL efflux capacity was directly associated with large (β = 0.037, P HDL particle concentration and inversely associated with small (β = -0.0049, P = 0.018) HDL particle concentration in multivariable adjusted models. HDL efflux capacity and HDL particle number were inversely associated with prevalent LRNC plaque in unadjusted models (odds ratio: 0.5; 95% confidence interval: 0.26, 0.96), but not after multivariable adjustment. HDL particle size was not associated with prevalent LRNC. HDL particle size was significantly associated with HDL efflux capacity, suggesting that differences in HDL efflux capacity may be due to structural differences in HDL particles. Future research is needed to determine whether HDL efflux is a marker of ASCVD risk in older populations.

  9. Determinants of HDL Cholesterol Efflux Capacity after Virgin Olive Oil Ingestion: Interrelationships With Fluidity of HDL Monolayer.

    Science.gov (United States)

    Fernández-Castillejo, Sara; Rubió, Laura; Hernáez, Álvaro; Catalán, Úrsula; Pedret, Anna; Valls, Rosa-M; Mosele, Juana I; Covas, Maria-Isabel; Remaley, Alan T; Castañer, Olga; Motilva, Maria-José; Solá, Rosa

    2017-09-08

    Cholesterol efflux capacity of HDL (CEC) is inversely associated with cardiovascular risk. HDL composition, fluidity, oxidation, and size are related with CEC. We aimed to assess which HDL parameters were CEC determinants after virgin olive oil (VOO) ingestion. Post-hoc analyses from the VOHF study, a crossover intervention with three types of VOO. We assessed the relationship of 3-week changes in HDL-related variables after intervention periods with independence of the type of VOO. After univariate analyses, mixed linear models were fitted with variables related with CEC and fluidity. Fluidity and Apolipoprotein (Apo)A-I content in HDL was directly associated, and HDL oxidative status inversely, with CEC. A reduction in free cholesterol, an increase in triglycerides in HDL, and a decrease in small HDL particle number or an increase in HDL mean size, were associated to HDL fluidity. HDL fluidity, ApoA-I concentration, and oxidative status are major determinants for CEC after VOO. The impact on CEC of changes in free cholesterol and triglycerides in HDL, and those of small HDL or HDL mean size, could be mechanistically linked through HDL fluidity. Our work points out novel therapeutic targets to improve HDL functionality in humans through nutritional or pharmacological interventions. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Generation of HDL models for bio-impedance sensor simulation based on microelectrodes

    OpenAIRE

    Yúfera, A.; Gallego, Estefanía

    2011-01-01

    This paper presents a computer tool for automatic analysis of cell culture images. The program allows the extraction of relevant information from biological images for pre and post system analysis. In particular, this tool is being used for electrical characterization of electrode-solution-cell systems in which bio-impedance is the main parameter to be known. The correct modeling of this kind of systems enables both electronic system characterization for circuit design specifications and data...

  11. Kinetics of prebeta1 HDL and alphaHDL in type II diabetic patients.

    Science.gov (United States)

    Chétiveaux, M; Lalanne, F; Lambert, G; Zair, Y; Ouguerram, K; Krempf, M

    2006-01-01

    The aim of this study was to analyze the recycling of high density lipoprotein (HDL) in six type II diabetic patients compared with six control subjects by endogenous labelling of apolipoprotein A-I (Apo A-I) with stable isotope Apo A. The -I-HDL kinetics were performed by infusion of (5.5.5-(2)H3)-leucine for 14 h. The prebeta1 and alphaHDL were separated by gel filtration fast protein liquid chromatrography system (FPLC). Kinetics of isotopic enrichment of Apo A-I were analyzed with a multi-compartmental model software (SAAM II, SAAM Institute, Seattle, WA). Plasma Apo A-I concentration was decreased in patients with type II diabetes as a result of a decrease in Apo A-I-alphaHDL (P Diabetic patients were also characterized by an increased relative contribution of Apo A-I in prebeta1 HDL (18.3 +/- 2.8% vs 11.9 +/- 3.7%, P HDL was slightly increased in diabetic patients compared with control (NS) and an increase of recycling rate of alpha to prebeta1 HDL was observed (11.67 +/- 3.14 d(-1) vs 7.09 +/- 4.51 d(-1), P diabetic patients (P HDL and P HDL in type II diabetic patients is mainly related to an increased conversion rate of alpha to prebeta1 HDL.

  12. Probing of Nascent Riboswitch Transcripts.

    Science.gov (United States)

    Chauvier, Adrien; Lafontaine, Daniel A

    2015-01-01

    The study of biologically significant and native structures is vital to characterize RNA-based regulatory mechanisms. Riboswitches are cis-acting RNA molecules that are involved in the biosynthesis and transport of cellular metabolites. Because riboswitches regulate gene expression by modulating their structure, it is vital to employ native probing assays to determine how native riboswitch structures perform highly efficient and specific ligand recognition. By employing RNase H probing, it is possible to determine the accessibility of specific RNA domains in various structural contexts. Herein, we describe how to employ RNase H probing to characterize nascent mRNA riboswitch molecules as a way to obtain information regarding the riboswitch regulation control mechanism.

  13. 干/湿纺制初生中空纤维膜数学模型的数值模拟%Numerical Simulation of a Mathematical Model for Dry/Wet-Spun Nascent Hollow Fiber Membrane

    Institute of Scientific and Technical Information of China (English)

    法德勒; 许振良

    2004-01-01

    In an effort to find the effect of mass transfer, surface tension and drag forces on the velocity distribution, the mathematical model of the velocity profile of a nascent hollow fiber during membrane formation in the air gap region was numerically simulated by using the Runge-Kutta method (fourth-order method). The effect of mass transfer on velocity distribution based on the complicated function (G(Ch8)) was presented and the effects of a complicated function were studied in two cases: in the first case, G (Ch8) was constant; in the second, G (Ch8) was variable. The latter was done by varying with the concentration of solvent in a nascent hollow fiber through the air-gap region. One empirical equation was used to describe this change and the predicted values had a better agreement with the experimental values. To verify the model hypotheses, hollow fiber membranes were spun from 20:80 polybenzimidazole/polyetherimide dopes with 25.6 wt% solid in N, N-dimethylacetamide (DMAc) using water as the external and internal coagulants. Based on the experimental results of dry-jet wet-spinning process for the fabrication of hollow fiber membranes, it is found that the model calculated values were in a good agreement with the experimental values.

  14. From nascent to actual entrepreneurship: the effect of entry barriers

    NARCIS (Netherlands)

    A.J. van Stel (André); D. Storey (David); A.R.M. Wennekers (Sander); A.R. Thurik (Roy)

    2005-01-01

    textabstractThis exploratory study focuses on the conversion from nascent to actual entrepreneurship and the role of entry barriers in this process. Using data for a sample of countries participating in the Global Entrepreneurship Monitor between 2002 and 2004, we estimate a twoequation model

  15. Curriculum evaluation and revision in a nascent field: the utility of the retrospective pretest--posttest model in a homeland security program of study.

    Science.gov (United States)

    Pelfrey, William V; Pelfrey, William V

    2009-02-01

    Although most academic disciplines evolve at a measured pace, the emerging field of homeland security must, for reasons of safety and security, evolve rapidly. The Department of Homeland Security sponsored the establishment of a graduate educational program for key officials holding homeland security roles. Because homeland security is a nascent field, the establishment of a program curriculum was forced to draw from a variety of disciplines. Curriculum evaluation was complicated by the rapid changes occurring in the emerging discipline, producing response shift bias, and interfering with the pre-post assessments. To compensate for the validity threat associated with response shift bias, a retrospective pretest-posttest evaluative methodology was used. Data indicate the program has evolved in a significant and orderly fashion and these data support the use of this innovative evaluation approach in the development of any discipline.

  16. Effect of spermine on lipid profile and HDL functionality in the streptozotocin-induced diabetic rat model.

    Science.gov (United States)

    Jafarnejad, A; Bathaie, S Z; Nakhjavani, M; Hassan, M Z

    2008-01-30

    This study aimed to investigate the effect of spermine (Spm) as a chemical chaperone and glycation inhibitor on the lipid profile and HDL functionality in the short- and long-term treatment of the STZ-induced diabetic rats. Male Wistar rats were divided into 4 groups (control, n=7; diabetic, n=9). Two groups (named 2 and 3) were injected intraperitoneally with streptozotocin. Control rats (named 1 and 4) were injected with vehicle alone. The treatment of diabetic and control animals (groups 3 and 4) with 60 micromol/l of Spm in drinking water was begun. The study continued up to the end of the fifth month. The serum glucose and insulin level, AGE formation, lipid profile, paraoxonase 1 (PON1), and lecithin: cholesterol acyl transferase (LCAT) activities were measured. Significantly lower plasma PON1, and LCAT activities and higher serum AGE, TG, TC and LDL-c, and lower HDL-c were seen in diabetic rats as compared to control groups (Pdiabetic groups decreased gradually after receiving Spm. In addition, due to Spm administration, an increase in the HDL-c level was observed after the first month of the experiment (Pdiabetic group that received Spm was significant after the second and the forth month of the experiment, Pdiabetic rats. Spermine, despite a lack of significant changes on glucose metabolism and insulin secretion, was found to improve diabetes complications.

  17. Dysfunctional HDL from HIV+ individuals promotes monocyte-derived foam cell formation in vitro.

    Science.gov (United States)

    Angelovich, Thomas A; Hearps, Anna C; Oda, Michael N; Borja, Mark S; Huynh, Diana; Homann, Stefanie; Jaworowski, Anthony; Kelesidis, Theodoros

    2017-09-18

    The role of HDL function in HIV-related atherosclerotic cardiovascular disease (CVD) is unclear. HDLs isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals (HDL) were assessed for HDL function and ability to promote monocyte-derived foam cell formation (MDFCF) (a key event in HIV-related CVD) ex vivo. Using an established in vitro model of atherogenesis and plasma samples from an established cross-sectional study of virologically-suppressed HIV+ males on stable effective antiretroviral therapy (ART) and with low CVD risk (median age: 42 years; n = 10), we explored the impact of native HDL [HIV(+)HDL] on MDFCF. In this exploratory study we selected HIV-HDL known to be dysfunctional based on two independent measures of impaired HDL function: a) antioxidant (high HDLox) b) ability of HDL to release apoA-I [low HDL-apoA-I exchange (HAE %)]. Five healthy males matched by age and race to the HIV+ group were included. Given that oxidation of HDL leads to abnormal HDL function, we also compared proatherogenic effects of HIV-HDL versus chemically-derived HDLox. The ex vivo atherogenesis assay was performed using lipoproteins (purchased or isolated from plasma using ultracentrifugation) and monocytes purified via negative selection from healthy donors. HIV(+)HDL known to have reduced antioxidant function and rate of HDL/ApoAI exchange promoted MDFCF to a greater extent than HDL (33.0% vs 26.2% foam cells; p = 0.015). HDL oxidized in vitro also enhanced foam cell formation as compared to non-oxidized HDL (p HDL in virologically suppressed HIV+ individuals may potentiate atherosclerosis in HIV infection by promoting monocyte-derived foam cell formation.The role of HDL function in HIV-related atherosclerotic cardiovascular disease is unclear. HDL isolated from HIV+ [HIV(+)HDL] and HIV-uninfected individuals [HIV(-)HDL] were assessed for HDL function and ability to promote foam cell formation ex vivo. HIV(+)HDL known to have reduced antioxidant function and

  18. Atomistic MD simulation reveals the mechanism by which CETP penetrates into HDL enabling lipid transfer from HDL to CETP

    Science.gov (United States)

    Cilpa-Karhu, Geraldine; Jauhiainen, Matti; Riekkola, Marja-Liisa

    2015-01-01

    Inhibition of cholesterol ester transfer protein (CETP), a protein mediating transfer of neutral lipids between lipoproteins, has been proposed as a means to elevate atheroprotective HDL subpopulations and thereby reduce atherosclerosis. However, off-target and adverse effects of the inhibition have raised doubts about the molecular mechanism of CETP-HDL interaction. Recent experimental findings have demonstrated the penetration of CETP into HDL. However, atomic level resolution of CETP penetration into HDL, a prerequisite for a better understanding of CETP functionality and HDL atheroprotection, is missing. We constructed an HDL particle that mimics the actual human HDL mass composition and investigated for the first time, by large-scale atomistic molecular dynamics, the interaction of an upright CETP with a human HDL-mimicking model. The results demonstrated how CETP can penetrate the HDL particle surface, with the formation of an opening in the N barrel domain end of CETP, put in evidence the major anchoring role of a tryptophan-rich region of this domain, and unveiled the presence of a phenylalanine barrier controlling further access of HDL-derived lipids to the tunnel of CETP. The findings reveal novel atomistic details of the CETP-HDL interaction mechanism and can provide new insight into therapeutic strategies. PMID:25424006

  19. Normal HDL-apo AI turnover and cholesterol enrichment of HDL subclasses in New Zealand rabbits with partial nephrectomy.

    Science.gov (United States)

    Toledo-Ibelles, Paola; Franco, Martha; Carreón-Torres, Elizabeth; Luc, Gérald; Tailleux, Anne; Vargas-Alarcón, Gilberto; Fragoso, José Manuel; Aguilar-Salinas, Carlos; Luna-Luna, María; Pérez-Méndez, Oscar

    2013-04-01

    The kidney has been proposed to play a central role in apo AI catabolism, suggesting that HDL structure is determined, at least in part, by this organ. Here, we aimed at determining the effects of a renal mass reduction on HDL size distribution, lipid content, and apo AI turnover. We characterized HDL subclasses in rabbits with a 75% reduction of functional renal mass (Nptx group), using enzymatic staining of samples separated on polyacrylamide electrophoresis gels, and also performed kinetic studies using radiolabeled HDL-apo AI in this animal model. Creatinine clearance was reduced to 35% after nephrectomy as compared to the basal values, but without increased proteinuria. A slight, but significant modification of the relative HDL size distribution was observed after nephrectomy, whereas cholesterol plasma concentrations gradually augmented from large HDL2b (+54%) to small HDL3b particles (+150%, Ptriglycerides of HDL subclasses were not affected by nephrectomy. HDL-apo AI fractional catabolic rates were similar to controls. Reduction of functional renal mass is associated to enrichment of HDL subclasses with cholesteryl esters. Structural abnormalities were not related to a low apo AI turnover, suggesting renal contribution to HDL remodeling beyond being just a catabolic site for these lipoproteins. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function.

    Science.gov (United States)

    Lê, Quang Huy; El Alaoui, Meddy; Véricel, Evelyne; Ségrestin, Bérénice; Soulère, Laurent; Guichardant, Michel; Lagarde, Michel; Moulin, Philippe; Calzada, Catherine

    2015-05-01

    High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). The objective of our study was to investigate the effects of in vitro glycoxidized HDL and HDL from patients with T2D on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Compared with control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to scavenger receptor BI (SR-BI). Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phosphatidylcholine (PC), namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE, and 15-HETE in phospholipids (2.1-, 2.1-, and 2.4-fold increase, respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Our results suggest that in vitro glycoxidized HDL as well as HDL from patients with T2D inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from patients with T2D.

  1. Glycoxidized HDL, HDL enriched with oxidized phospholipids and HDL from diabetic patients inhibit platelet function

    Science.gov (United States)

    Lê, Quang Huy; El Alaoui, Meddy; Véricel, Evelyne; Ségrestin, Bérénice; Soulère, Laurent; Guichardant, Michel; Lagarde, Michel; Moulin, Philippe; Calzada, Catherine

    2015-01-01

    Context High-density lipoproteins (HDL) possess atheroprotective properties including anti-thrombotic and antioxidant effects. Very few studies relate to the functional effects of oxidized HDL on platelets in type 2 diabetes (T2D). Objective The objective of our study was to investigate the effects of in vitro glycoxidized HDL, and HDL from T2D patients on platelet aggregation and arachidonic acid signaling cascade. At the same time, the contents of hydroxylated fatty acids were assessed in HDL. Results Compared to control HDL, in vitro glycoxidized HDL had decreased proportions of linoleic (LA) and arachidonic (AA) acids in phospholipids and cholesteryl esters, and increased concentrations of hydroxy-octadecadienoic acids (9-HODE and 13-HODE) and 15-hydroxy-eicosatetraenoic acid (15-HETE), derived from LA and AA respectively, especially hydroxy derivatives esterified in phospholipids. Glycoxidized HDL dose-dependently decreased collagen-induced platelet aggregation by binding to SR-BI. Glycoxidized HDL prevented collagen-induced increased phosphorylation of platelet p38 MAPK and cytosolic phospholipase A2, as well as intracellular calcium mobilization. HDL enriched with oxidized phospholipids, namely PC(16:0/13-HODE) dose-dependently inhibited platelet aggregation. Increased concentrations of 9-HODE, 13-HODE and 15-HETE in phospholipids (2.1, 2.1 and 2.4-fold increase respectively) were found in HDL from patients with T2D, and these HDL also inhibited platelet aggregation via SR-BI. Conclusions Altogether, our results indicate that in vitro glycoxidized HDL as well as HDL from T2D patients inhibit platelet aggregation, and suggest that oxidized LA-containing phospholipids may contribute to the anti-aggregatory effects of glycoxidized HDL and HDL from T2D patients. PMID:25794249

  2. HDL in diabetic nephropathy has less effect in endothelial repairing than diabetes without complications.

    Science.gov (United States)

    Li, Yufeng; Zhao, Mingming; He, Dan; Zhao, Xuyang; Zhang, Wenjing; Wei, Lixin; Huang, Edgar; Ji, Liang; Zhang, Meng; Willard, Belinda; Fu, Zuodi; Wang, Lijuan; Pan, Bing; Zheng, Lemin; Ji, Linong

    2016-04-14

    Diabetic nephropathy has a high cardiovascular risk with a low-level HDL(high density lipoprotein) in epidemiologic studies. Glycated HDL in diabetes can diminish the capacity to stimulate endothelial cell migration, but the mechanism has not been adequately explored in diabetic nephropathy. We performed this study to find out whether HDL in diabetic nephropathy is more dysfunctional than HDL in diabetes without complications. Endothelial cells were treated with N-HDL (normal), D-HDL (T2DM[type 2 diabetes mellitus] without complications), DN-HDL (T2DM nephropathy), N-apoA-I (normal apoA-I), and G-apoA-I (glycated apoA-I in vitro). Cell migration capacity was measured with wound-healing and transwell migration assay in vitro and electric carotid injury model in vivo. Protein glycation levels were measured with nanoLC-MS/MS. PI3K expression and Akt phosphorylation were analyzed by western blot. In wound-healing assay, DN-HDL showed a 17.12% decrease compared with D-HDL (p HDL showed a 29.85% decrease in comparison with D-HDL (p HDL and DN-HDL impaired the re-endothelialization capacity; DN-HDL was less effective than D-HDL. Meanwhile, DN-HDL was found to have a significantly higher protein glycation level than D-HDL (p HDL in comparison with D-HDL and N-HDL. We found that HDL from diabetic nephropathy has a higher level of glycation and induced less cell migration in vitro and in vivo compared with that from diabetes without nephropathy. This finding suggests that diabetic nephropathy has higher levels of glycated HDL and partially explains why patients with DN have a higher risk of cardiovascular disease.

  3. LDL and HDL subfractions, dysfunctional HDL: treatment options.

    Science.gov (United States)

    Garcia-Rios, Antonio; Nikolic, Dragana; Perez-Martinez, Pablo; Lopez-Miranda, Jose; Rizzo, Manfredi; Hoogeveen, Ron C

    2014-01-01

    Low-density lipoproteins (LDL) are considered as important risk factors for cardiovascular diseases (CVD), while highdensity lipoproteins (HDL) are well recognized for their putative role in reverse cholesterol transport and other atheroprotective functions. Both LDL and HDL are heterogeneous in nature, including various subfractions depending on the method of isolation (≥ 7 LDL and 10 HDL subspecies, respectively). While it is established that small, dense LDL (sdLDL) have atherogenic potential, the role of different HDL subfractions is still largely unclear. The majority of clinical studies suggest an atheroprotective role of larger HDL particles, although recent work has highlighted the role of dysfunctional HDL within different subfractions. Several therapeutic approaches are able to primarily target cholesterol concentration in LDL or HDL. Certain drugs, such as niacin, statins and fibrates target multiple lipid traits (i.e. pleiotropic drug effects), while cholesterol ester transfer protein (CETP) inhibitors are able to increase plasma HDL cholesterol levels. Statins represent the most used lipid-lowering drugs, but there is a continued interest in the development of novel therapeutic approaches, including those that might affect dysfunctional HDL. Targeting distinct LDL and HDL subfractions may potentially reduce the residual risk seen in clinical endpoint trials.

  4. HDL, Atherosclerosis, and Emerging Therapies

    Science.gov (United States)

    Genest, Jacques

    2013-01-01

    This review aims to provide an overview on the properties of high-density lipoproteins (HDLs) and their cardioprotective effects. Emergent HDL therapies will be presented in the context of the current understanding of HDL function, metabolism, and protective antiatherosclerotic properties. The epidemiological association between levels of HDL-C or its major apolipoprotein (apoA-I) is strong, graded, and coherent across populations. HDL particles mediate cellular cholesterol efflux, have antioxidant properties, and modulate vascular inflammation and vasomotor function and thrombosis. A link of causality has been cast into doubt with Mendelian randomization data suggesting that genes causing HDL-C deficiency are not associated with increased cardiovascular risk, nor are genes associated with increased HDL-C, with a protective effect. Despite encouraging data from small studies, drugs that increase HDL-C levels have not shown an effect on major cardiovascular end-points in large-scale clinical trials. It is likely that the cholesterol mass within HDL particles is a poor biomarker of therapeutic efficacy. In the present review, we will focus on novel therapeutic avenues and potential biomarkers of HDL function. A better understanding of HDL antiatherogenic functions including reverse cholesterol transport, vascular protective and antioxidation effects will allow novel insight on novel, emergent therapies for cardiovascular prevention. PMID:23781332

  5. Deciphering Transcriptional Dynamics In Vivo by Counting Nascent RNA Molecules.

    Science.gov (United States)

    Choubey, Sandeep; Kondev, Jane; Sanchez, Alvaro

    2015-11-01

    Deciphering how the regulatory DNA sequence of a gene dictates its expression in response to intra and extracellular cues is one of the leading challenges in modern genomics. The development of novel single-cell sequencing and imaging techniques, as well as a better exploitation of currently available single-molecule imaging techniques, provides an avenue to interrogate the process of transcription and its dynamics in cells by quantifying the number of RNA polymerases engaged in the transcription of a gene (or equivalently the number of nascent RNAs) at a given moment in time. In this paper, we propose that measurements of the cell-to-cell variability in the number of nascent RNAs provide a mostly unexplored method for deciphering mechanisms of transcription initiation in cells. We propose a simple kinetic model of transcription initiation and elongation from which we calculate nascent RNA copy-number fluctuations. To demonstrate the usefulness of this approach, we test our theory against published nascent RNA data for twelve constitutively expressed yeast genes. Rather than transcription being initiated through a single rate limiting step, as it had been previously proposed, our single-cell analysis reveals the presence of at least two rate limiting steps. Surprisingly, half of the genes analyzed have nearly identical rates of transcription initiation, suggesting a common mechanism. Our analytical framework can be used to extract quantitative information about dynamics of transcription from single-cell sequencing data, as well as from single-molecule imaging and electron micrographs of fixed cells, and provides the mathematical means to exploit the quantitative power of these technologies.

  6. Deciphering Transcriptional Dynamics In Vivo by Counting Nascent RNA Molecules.

    Directory of Open Access Journals (Sweden)

    Sandeep Choubey

    2015-11-01

    Full Text Available Deciphering how the regulatory DNA sequence of a gene dictates its expression in response to intra and extracellular cues is one of the leading challenges in modern genomics. The development of novel single-cell sequencing and imaging techniques, as well as a better exploitation of currently available single-molecule imaging techniques, provides an avenue to interrogate the process of transcription and its dynamics in cells by quantifying the number of RNA polymerases engaged in the transcription of a gene (or equivalently the number of nascent RNAs at a given moment in time. In this paper, we propose that measurements of the cell-to-cell variability in the number of nascent RNAs provide a mostly unexplored method for deciphering mechanisms of transcription initiation in cells. We propose a simple kinetic model of transcription initiation and elongation from which we calculate nascent RNA copy-number fluctuations. To demonstrate the usefulness of this approach, we test our theory against published nascent RNA data for twelve constitutively expressed yeast genes. Rather than transcription being initiated through a single rate limiting step, as it had been previously proposed, our single-cell analysis reveals the presence of at least two rate limiting steps. Surprisingly, half of the genes analyzed have nearly identical rates of transcription initiation, suggesting a common mechanism. Our analytical framework can be used to extract quantitative information about dynamics of transcription from single-cell sequencing data, as well as from single-molecule imaging and electron micrographs of fixed cells, and provides the mathematical means to exploit the quantitative power of these technologies.

  7. Therapeutic potential of HDL in cardioprotection and tissue repair.

    Science.gov (United States)

    Van Linthout, Sophie; Frias, Miguel; Singh, Neha; De Geest, Bart

    2015-01-01

    Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes. HDL may improve cardiac function in several ways. Firstly, HDL may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. Secondly, HDL can improve cardiac function in the absence of ischaemic heart disease as illustrated by beneficial effects conferred by these lipoproteins in diabetic cardiomyopathy. Thirdly, HDL may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodelling post-myocardial infarction. These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied treatment with native HDL, treatment with reconstituted HDL, or human apo A-I gene transfer. The effect of human apo A-I gene transfer on infarct expansion and ventricular remodelling post-myocardial infarction illustrates the beneficial effects of HDL on tissue repair. The role of HDL in tissue repair is further underpinned by the potent effects of these lipoproteins on endothelial progenitor cell number, function, and incorporation, which may in particular be relevant under conditions of high endothelial cell turnover. Furthermore, topical HDL therapy enhances cutaneous wound healing in different models. In conclusion, the development of HDL-targeted interventions in these strategically chosen therapeutic areas is supported by a strong clinical rationale and significant preclinical data.

  8. Folding at the birth of the nascent chain: coordinating translation with co-translational folding.

    Science.gov (United States)

    Zhang, Gong; Ignatova, Zoya

    2011-02-01

    In the living cells, the folding of many proteins is largely believed to begin co-translationally, during their biosynthesis at the ribosomes. In the ribosomal tunnel, the nascent peptide may establish local interactions and stabilize α-helical structures. Long-range contacts are more likely outside the ribosomes after release of larger segments of the nascent chain. Examples suggest that domains can attain native-like structure on the ribosome with and without population of folding intermediates. The co-translational folding is limited by the speed of the gradual extrusion of the nascent peptide which imposes conformational restraints on its folding landscape. Recent experimental and in silico modeling studies indicate that translation kinetics fine-tunes co-translational folding by providing a time delay for sequential folding of distinct portions of the nascent chain.

  9. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen

    2009-11-01

    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  10. Computer arithmetic and verilog HDL fundamentals

    CERN Document Server

    Cavanagh, Joseph

    2009-01-01

    Verilog Hardware Description Language (HDL) is the state-of-the-art method for designing digital and computer systems. Ideally suited to describe both combinational and clocked sequential arithmetic circuits, Verilog facilitates a clear relationship between the language syntax and the physical hardware. It provides a very easy-to-learn and practical means to model a digital system at many levels of abstraction. Computer Arithmetic and Verilog HDL Fundamentals details the steps needed to master computer arithmetic for fixed-point, decimal, and floating-point number representations for all prima

  11. Enhanced HDL Functionality in Small HDL Species Produced Upon Remodeling of HDL by Reconstituted HDL, CSL112

    Science.gov (United States)

    Didichenko, Svetlana A.; Navdaev, Alexei V.; Cukier, Alexandre M.O.; Gille, Andreas; Schuetz, Patrick; Spycher, Martin O.; Thérond, Patrice; Chapman, M. John; Kontush, Anatol

    2016-01-01

    Rationale: CSL112, human apolipoprotein A-I (apoA-I) reconstituted with phosphatidylcholine, is known to cause a dramatic rise in small high-density lipoprotein (HDL). Objective: To explore the mechanisms by which the formation of small HDL particles is induced by CSL112. Methods and Results: Infusion of CSL112 into humans caused elevation of 2 small diameter HDL fractions and 1 large diameter fraction. Ex vivo studies showed that this remodeling does not depend on lipid transfer proteins or lipases. Rather, interaction of CSL112 with purified HDL spontaneously gave rise to 3 HDL species: a large, spherical species composed of apoA-I from native HDL and CSL112; a small, disc-shaped species composed of apoA-I from CSL112, but smaller because of the loss of phospholipids; and the smallest species, lipid-poor apoA-I composed of apoA-I from HDL and CSL112. Time-course studies suggest that remodeling occurs by an initial fusion of CSL112 with HDL and subsequent fission leading to the smaller forms. Functional studies showed that ATP-binding cassette transporter 1–dependent cholesterol efflux and anti-inflammatory effects in whole blood were carried by the 2 small species with little activity in the large species. In contrast, the ability to inactivate lipid hydroperoxides in oxidized low-density lipoprotein was carried predominantly by the 2 largest species and was low in lipid-poor apoA-I. Conclusions: We have described a mechanism for the formation of small, highly functional HDL species involving spontaneous fusion of discoidal HDL with spherical HDL and subsequent fission. Similar remodeling is likely to occur during the life cycle of apoA-I in vivo. PMID:27436846

  12. Three-dimensional modeling of oxidized-LDL accumulation and HDL mass transport in a coronary artery: a proof-of-concept study for predicting the region of atherosclerotic plaque development.

    Science.gov (United States)

    Sakellarios, Antonis I; Siogkas, Panagiotis K; Athanasiou, Lambros S; Exarchos, Themis P; Papafaklis, Michail I; Bourantas, Christos V; Naka, Katerina K; Michalis, Lampros K; Filipovic, Nenad; Parodi, Oberdan; Fotiadis, Dimitrios I

    2013-01-01

    Low density lipoprotein (LDL) has a significant role on the atherosclerotic plaque development, while the concentration of high density lipoproteins (HDL) is considered to play an atheroprotective role according to several biochemical mechanisms. In this work, it is the first time that both LDL and HDL concentrations are taken into account in order to predict the regions prone for plaque development. Our modeling approach is based on the use of a realistic three-dimensional reconstructed pig coronary artery in two time points. Biochemical data measured in the pig were also included in order to develop a more customized model. We modeled coronary blood flow by solving the Navier-Stokes equations in the arterial lumen and plasma filtration in the arterial wall using Darcy's Law. HDL transport was modeled only in the arterial lumen using the convection-diffusion equation, while LDL transport was modeled both in the lumen and the arterial wall. An additional novelty of this work is that we model the oxidation of LDL taking into account the atheroprotective role of HDL. The results of our model were in good agreement with histological findings demonstrating that increased oxidized LDL is found near regions of advanced plaques, while non-oxidized LDL is found in regions of early plaque types.

  13. The Biogenesis of Nascent Circular RNAs

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2016-04-01

    Full Text Available Steady-state circular RNAs (circRNAs have been mapped to thousands of genomic loci in mammals. We studied circRNA processing using metabolic tagging of nascent RNAs with 4-thiouridine (4sU. Strikingly, the efficiency of circRNA processing from pre-mRNA is extremely low endogenously. Additional studies revealed that back-splicing outcomes correlate with fast RNA Polymerase II elongation rate and are tightly controlled by cis-elements in vivo. Additionally, prolonged 4sU labeling in cells shows that circRNAs are largely processed post-transcriptionally and that circRNAs are stable. Circular RNAs that are abundant at a steady-state level tend to accumulate. This is particularly true in cells, such as neurons, that have slow division rates. This study uncovers features of circRNA biogenesis by investigating the link between nascent circRNA processing and transcription.

  14. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andrew A. Bremer

    2013-01-01

    Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

  15. Genetics Home Reference: familial HDL deficiency

    Science.gov (United States)

    ... Genetics Home Health Conditions familial HDL deficiency familial HDL deficiency Enable Javascript to view the expand/collapse ... Download PDF Open All Close All Description Familial HDL deficiency is a condition characterized by low levels ...

  16. Beyond HDL-cholesterol increase: phospholipid enrichment and shift from HDL3 to HDL2 in alcohol consumers

    DEFF Research Database (Denmark)

    Schäfer, C.; Parlesak, Alexandr; Eckoldt, J.;

    2007-01-01

    The reduction of cardiovascular mortality associated with moderate alcohol consumption is chiefly thought to be mediated by an increase of high density lipoprotein cholesterol (HDL-CH). This study highlights additional qualitative changes of HDL that might augment this antiatherogenic effect...... HDL(2a), HDL(2b), and HDL(3). No difference in LDL-cholesterol was observed. Compared with group 1, groups 2 and 3 exhibited significant increases of HDL-CH (group 1, 44 +/- 10 mg/dl; group 2, 51 +/- 11 mg/dl; group 3, 55 +/- 11 mg/dl; mean +/- SD, PHDL...... (increase of the HDL(2)-CH/HDL(3)-CH ratio). Moreover, phospholipid enrichment of HDL occurred in alcohol consumers, whereas the ratios between other HDL components remained constant. Multivariate analysis revealed alcohol to have the foremost statistical influence on changes of the HDL fraction, followed...

  17. HDL and atherosclerotic cardiovascular disease: genetic insights into complex biology.

    Science.gov (United States)

    Rosenson, Robert S; Brewer, H Bryan; Barter, Philip J; Björkegren, Johan L M; Chapman, M John; Gaudet, Daniel; Kim, Daniel Seung; Niesor, Eric; Rye, Kerry-Anne; Sacks, Frank M; Tardif, Jean-Claude; Hegele, Robert A

    2017-08-10

    Plasma levels of HDL cholesterol (HDL-C) predict the risk of cardiovascular disease at the epidemiological level, but a direct causal role for HDL in cardiovascular disease remains controversial. Studies in animal models and humans with rare monogenic disorders link only particular HDL-associated mechanisms with causality, including those mechanisms related to particle functionality rather than cholesterol content. Mendelian randomization studies indicate that most genetic variants that affect a range of pathways that increase plasma HDL-C levels are not usually associated with reduced risk of cardiovascular disease, with some exceptions, such as cholesteryl ester transfer protein variants. Furthermore, only a fraction of HDL-C variation has been explained by known loci from genome-wide association studies (GWAS), suggesting the existence of additional pathways and targets. Systems genetics can enhance our understanding of the spectrum of HDL pathways, particularly those pathways that involve new and non-obvious GWAS loci. Bioinformatic approaches can also define new molecular interactions inferred from both large-scale genotypic data and RNA sequencing data to reveal biologically meaningful gene modules and networks governing HDL metabolism with direct relevance to disease end points. Targeting these newly recognized causal networks might inform the development of novel therapeutic strategies to reduce the risk of cardiovascular disease.

  18. ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

    Science.gov (United States)

    Cedó, Lídia; García-León, Annabel; Baila-Rueda, Lucía; Santos, David; Grijalva, Victor; Martínez-Cignoni, Melanie Raquel; Carbó, José M.; Metso, Jari; López-Vilaró, Laura; Zorzano, Antonio; Valledor, Annabel F.; Cenarro, Ana; Jauhiainen, Matti; Lerma, Enrique; Fogelman, Alan M.; Reddy, Srinivasa T.; Escolà-Gil, Joan Carles; Blanco-Vaca, Francisco

    2016-01-01

    Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification. PMID:27808249

  19. A conversation with 590 nascent entrepreneurs

    OpenAIRE

    Campbell, Jeffrey R.; De Nardi, Mariacristina

    2007-01-01

    This paper summarizes interviews from 1998 with 590 individuals trying to create a business centered around five questions: “Who are you?”, “What are you trying to accomplish?”, “What have you and others put into the business?”, “What have you accomplished?”, “What remains to be done?” There is a great deal of heterogeneity across these Nascent entrepreneurs, but they tend to have more education than the general population. Growing up in a family in which one or both parents had a business do...

  20. HDL to verification logic translator

    Science.gov (United States)

    Gambles, J. W.; Windley, P. J.

    The increasingly higher number of transistors possible in VLSI circuits compounds the difficulty in insuring correct designs. As the number of possible test cases required to exhaustively simulate a circuit design explodes, a better method is required to confirm the absence of design faults. Formal verification methods provide a way to prove, using logic, that a circuit structure correctly implements its specification. Before verification is accepted by VLSI design engineers, the stand alone verification tools that are in use in the research community must be integrated with the CAD tools used by the designers. One problem facing the acceptance of formal verification into circuit design methodology is that the structural circuit descriptions used by the designers are not appropriate for verification work and those required for verification lack some of the features needed for design. We offer a solution to this dilemma: an automatic translation from the designers' HDL models into definitions for the higher-ordered logic (HOL) verification system. The translated definitions become the low level basis of circuit verification which in turn increases the designer's confidence in the correctness of higher level behavioral models.

  1. HDL to verification logic translator

    Science.gov (United States)

    Gambles, J. W.; Windley, P. J.

    1992-01-01

    The increasingly higher number of transistors possible in VLSI circuits compounds the difficulty in insuring correct designs. As the number of possible test cases required to exhaustively simulate a circuit design explodes, a better method is required to confirm the absence of design faults. Formal verification methods provide a way to prove, using logic, that a circuit structure correctly implements its specification. Before verification is accepted by VLSI design engineers, the stand alone verification tools that are in use in the research community must be integrated with the CAD tools used by the designers. One problem facing the acceptance of formal verification into circuit design methodology is that the structural circuit descriptions used by the designers are not appropriate for verification work and those required for verification lack some of the features needed for design. We offer a solution to this dilemma: an automatic translation from the designers' HDL models into definitions for the higher-ordered logic (HOL) verification system. The translated definitions become the low level basis of circuit verification which in turn increases the designer's confidence in the correctness of higher level behavioral models.

  2. A Comparison of the Theoretical Relationship between HDL Size and the Ratio of HDL Cholesterol to Apolipoprotein A-I with Experimental Results from the Women’s Health Study

    Science.gov (United States)

    Mazer, Norman A.; Giulianini, Franco; Paynter, Nina P.; Jordan, Paul; Mora, Samia

    2013-01-01

    Background HDL size and composition vary among individuals and may be associated with cardiovascular disease and diabetes. We investigated the theoretical relationship between HDL size and composition using an updated version of the spherical model of lipoprotein structure proposed by Shen et al. and compared its predictions with experimental data from the Women’s Health Study (WHS). Methods The Shen model was updated to predict the relationship between HDL diameter and the ratio of HDL-cholesterol (HDL-C) to apolipoprotein A-I (ApoA-I) plasma concentrations, i.e., the HDL-C/ApoA-I ratio. In WHS (n=26,772), NMR spectroscopy was used to measure the average HDL diameter (davg,NMR) and particle concentration (HDL-P); HDL-C and ApoA-I (mg/dL) were measured by standardized assays. Results The updated Shen model predicts a quasi-linear increase of HDL diameter with the HDL-C/ApoA-I ratio, consistent with the measured davg,NMR values from WHS, which ranged between 8.0 and 10.8 nm and correlated positively with the HDL-C/ApoA-I ratio (r=0.608, pHDL-C/ApoA-I. The validity of this equation for estimating HDL size was assessed with data from CETP deficiency and pharmacologic inhibition. We also illustrate how HDL-P can be estimated from the HDL size and ApoA-I level. Conclusions This study provides a large-scale experimental examination of the updated Shen model, offers new insights into HDL structure, composition and remodeling, and suggests that the HDL-C/ApoA-I ratio could be a readily available biomarker for estimating HDL size and HDL-P. PMID:23426429

  3. Modeling biology with HDL languages: a first step toward a genetic design automation tool inspired from microelectronics.

    Science.gov (United States)

    Gendrault, Yves; Madec, Morgan; Lallement, Christophe; Haiech, Jacques

    2014-04-01

    Nowadays, synthetic biology is a hot research topic. Each day, progresses are made to improve the complexity of artificial biological functions in order to tend to complex biodevices and biosystems. Up to now, these systems are handmade by bioengineers, which require strong technical skills and leads to nonreusable development. Besides, scientific fields that share the same design approach, such as microelectronics, have already overcome several issues and designers succeed in building extremely complex systems with many evolved functions. On the other hand, in systems engineering and more specifically in microelectronics, the development of the domain has been promoted by both the improvement of technological processes and electronic design automation tools. The work presented in this paper paves the way for the adaptation of microelectronics design tools to synthetic biology. Considering the similarities and differences between the synthetic biology and microelectronics, the milestones of this adaptation are described. The first one concerns the modeling of biological mechanisms. To do so, a new formalism is proposed, based on an extension of the generalized Kirchhoff laws to biology. This way, a description of all biological mechanisms can be made with languages widely used in microelectronics. Our approach is therefore successfully validated on specific examples drawn from the literature.

  4. HDL cholesterol, size, particle number, and residual vascular risk after potent statin therapy

    Science.gov (United States)

    Mora, Samia; Glynn, Robert J.; Ridker, Paul M

    2013-01-01

    Background Chemically-measured high-density lipoprotein cholesterol (HDL-C) may not be the best clinical measure of HDL. Little is known about alternative HDL meassures such as HDL size or particle number (HDL-P) as determinants of residual risk after potent statin therapy. Methods and Results In JUPITER, HDL size and HDL-P were measured by nuclear magnetic resonance spectroscopy, and HDL-C and apolipoprotein A-I (apoA-I) were chemically assayed in 10,886 participants without cardiovascular disease (CVD) before and after random allocation to rosuvastatin 20 mg/day or placebo. Levels were examined with first CVD (N=234). HDL-P correlated better with apoA-I (Spearman r=0.69, pHDL-C (r=0.55, pHDL-C (6.1%), apoA-I (2.1%), HDL-P (3.8%) and HDL size (1.2%); all pHDL-C, apoA-I, and HDL-P had similar inverse associations with CVD (risk factor-adjusted hazard ratio and 95% CI per 1-SD: 0.79 [0.63–0.98], 0.75 [0.62–0.92], and 0.81 [0.67–0.97], respectively). Among rosuvastatin-allocated individuals, on-treatment HDL-P had a statistically significant and somewhat stronger association with CVD (0.73, 0.57–0.93, p=0.01) than HDL-C (0.82, 0.63–1.08, p=0.16) or apoA-I (0.86, 0.67–1.10, p=0.22). Among rosuvastatin-allocated individuals, on-treatment HDL-P remained significant (0.72, 0.53–0.97, p=0.03) after additionally adjusting for HDL-C. In risk factor-adjusted models, HDL size showed no significant association with CVD. Conclusions In the setting of potent statin therapy, HDL particle number may be a better marker of residual risk than chemically-measured HDL-C or apoA-I. This has potential implications for evaluating novel therapies targeting HDL. Clinical Trial Registration ClinicalTrials.gov; NCT00239681 PMID:24002795

  5. Protective Effects of HDL Against Ischemia/Reperfusion Injury.

    Science.gov (United States)

    Gomaraschi, Monica; Calabresi, Laura; Franceschini, Guido

    2016-01-01

    Several lines of evidence suggest that, besides being a strong independent predictor of the occurrence of primary coronary events, a low plasma high density lipoprotein (HDL) cholesterol level is also associated with short- and long-term unfavorable prognosis in patients, who have recovered from a myocardial infarction, suggesting a direct detrimental effect of low HDL on post-ischemic myocardial function. Experiments performed in ex vivo and in vivo models of myocardial ischemia/reperfusion (I/R) injury have clearly shown that HDL are able to preserve cardiac function when given before ischemia or at reperfusion; the protective effects of HDL against I/R injury have been also confirmed in other tissues and organs, as brain and hind limb. HDL were shown to act on coronary endothelial cells, by limiting the increase of endothelium permeability and promoting vasodilation and neoangiogenesis, on white blood cells, by reducing their infiltration into the ischemic tissue and the release of pro-inflammatory and matrix-degrading molecules, and on cardiomyocytes, by preventing the activation of the apoptotic cascade. Synthetic HDL retains the cardioprotective activity of plasma-derived HDL and may become a useful adjunctive therapy to improve clinical outcomes in patients with acute coronary syndromes or undergoing coronary procedures.

  6. Implementation of Secured Car Parking Management System Using Verilog HDL

    Directory of Open Access Journals (Sweden)

    Bhavana CHENDIKA

    2015-07-01

    Full Text Available Present days usage of motor vehicles are increased day by day, it causes the pollution, traffic congestion and parking place problems. In this paper we proposed a secured car parking management system using Verilog HDL. This system has two main modules Module-1: Slot identification for parking and LCD display screens, Module-2: Security indicator will provide security to the car, if unauthorized person want to vacant the car. These modules are modeled in Verilog HDL and implemented on FPGA.

  7. Seipin is required for converting nascent to mature lipid droplets

    DEFF Research Database (Denmark)

    Wang, Huajin; Becuwe, Michel; Housden, Benjamin E;

    2016-01-01

    How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation-the conversion of small, nascent LDs to larger, mature LDs. Seipin...... forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually...... leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent...

  8. HDL cholesterol: atherosclerosis and beyond

    NARCIS (Netherlands)

    Bochem, A.E.

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL

  9. Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy

    Science.gov (United States)

    McCormick, K. M.; Schultz, E.

    1992-01-01

    This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another

  10. Mechanisms of nascent fiber formation during avian skeletal muscle hypertrophy

    Science.gov (United States)

    McCormick, K. M.; Schultz, E.

    1992-01-01

    This study examined two putative mechanisms of new fiber formation in postnatal skeletal muscle, namely longitudinal fragmentation of existing fibers and de novo formation. The relative contributions of these two mechanisms to fiber formation in hypertrophying anterior latissimus dorsi (ALD) muscle were assessed by quantitative analysis of their nuclear populations. Muscle hypertrophy was induced by wing-weighting for 1 week. All nuclei formed during the weighting period were labeled by continuous infusion of 5-bromo-2'-deoxyuridine (BrdU), a thymidine analog, and embryonic-like fibers were identified using an antibody to ventricular-like embryonic (V-EMB) myosin. The number of BrdU-labeled and unlabeled nuclei in V-EMB-positive fibers were counted. Wing-weighting resulted in significant muscle enlargement and the appearance of many V-EMB+ fibers. The majority of V-EMB+ fibers were completely independent of mature fibers and had a nuclear density characteristics of developing fibers. Furthermore, nearly 100% of the nuclei in independent V-EMB+ fibers were labeled. These findings strongly suggest that most V-EMB+ fibers were nascent fibers formed de novo during the weighting period by satellite cell activation and fusion. Nascent fibers were found primarily in the space between fascicles where they formed a complex anastomosing network of fibers running at angles to one another. Although wing-weighting induced an increase in the number of branched fibers, there was no evidence that V-EMB+ fibers were formed by longitudinal fragmentation. The location of newly formed fibers in wing-weighted and regenerating ALD muscle was compared to determine whether satellite cells in the ALD muscle were unusual in that, if stimulated to divide, they would form fibers in the inter- and intrafascicular space. In contrast to wing-weighted muscle, nascent fibers were always found closely associated with necrotic fibers. These results suggest that wing-weighting is not simply another

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2003-12-01

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

  12. HDL cholesterol: reappraisal of its clinical relevance.

    Science.gov (United States)

    März, Winfried; Kleber, Marcus E; Scharnagl, Hubert; Speer, Timotheus; Zewinger, Stephen; Ritsch, Andreas; Parhofer, Klaus G; von Eckardstein, Arnold; Landmesser, Ulf; Laufs, Ulrich

    2017-03-24

    While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted. This review article is based on a selective literature review. In individuals without a history of cardiovascular events, low concentrations of HDL-C are inversely associated with the risk of future cardiovascular events. This relationship may, however, not apply to patients with metabolic disorders or manifest cardiovascular disease. The classical function of HDL is to mobilise cholesterol from extrahepatic tissues for delivery to the liver for excretion. These roles in cholesterol metabolism as well as many other biological functions of HDL particles are dependent on the number as well as protein and lipid composition of HDL particles. They are poorly reflected by the HDL-C concentration. HDL can even exert negative vascular effects, if its composition is pathologically altered. High serum HDL-C is therefore no longer regarded protective. In line with this, recent pharmacological approaches to raise HDL-C concentration have not been able to show reductions of cardiovascular outcomes. In contrast to LDL cholesterol (LDL-C), HDL-C correlates with cardiovascular risk only in healthy individuals. The calculation of the ratio of LDL-C to HDL-C is not useful for all patients. Low HDL-C should prompt examination of additional metabolic and inflammatory pathologies. An increase in HDL-C through lifestyle change (smoking cessation, physical exercise) has positive effects and is recommended. However, HDL-C is currently not a valid target for drug therapy.

  13. Novel pathways of apolipoprotein A-I metabolism in HDL of different sizes in humans

    Science.gov (United States)

    Mendivil, Carlos O.; Furtado, Jeremy; Morton, Allyson M.; Wang, Liyun; Sacks, Frank M.

    2015-01-01

    Objective A prevailing concept is that HDL is secreted into the systemic circulation as a small mainly discoidal particle; which expands progressively and becomes spherical by uptake and esterification of cellular cholesterol; and then contracts by cholesterol ester delivery to the liver, a process known as reverse cholesterol transport, thought to be impaired in people with low HDL cholesterol (HDLc). This metabolic framework has not been established in humans. Approach and results We studied the metabolism of apolipoproteinA-I in four standard HDL sizes by endogenous isotopic labeling in six overweight adults with low HDLc and in six adults with normal body weight with high plasma HDLc. Contrary to expectation, HDL was secreted into the circulation in its entire size distribution from very small to very large, similarly in both groups. Very small (prebeta) HDL comprised only 8% of total apoA-I secretion. Each HDL subfraction circulated mostly within its secreted size range for 1–4 days, and then was cleared. Enlargement of very small and medium to large and very large HDL, and generation of very small from medium HDL were minor metabolic pathways. Prebeta HDL was cleared slower whereas medium, large and very large HDL were cleared faster in the low HDLc group. Conclusions A new model is proposed from these results in which HDL is metabolized in plasma mainly within several discrete, stable sizes, across the common range of HDLc concentrations. PMID:26543096

  14. Translation regulation via nascent polypeptide-mediated ribosome stalling.

    Science.gov (United States)

    Wilson, Daniel N; Arenz, Stefan; Beckmann, Roland

    2016-04-01

    As the nascent polypeptide chain is being synthesized, it passes through a tunnel within the large ribosomal subunit. Interaction between the nascent polypeptide chain and the ribosomal tunnel can modulate the translation rate and induce translational stalling to regulate gene expression. In this article, we highlight recent structural insights into how the nascent polypeptide chain, either alone or in cooperation with co-factors, can interact with components of the ribosomal tunnel to regulate translation via inactivating the peptidyltransferase center of the ribosome and inducing ribosome stalling.

  15. Effects of curcumin on HDL functionality.

    Science.gov (United States)

    Ganjali, Shiva; Blesso, Christopher N; Banach, Maciej; Pirro, Matteo; Majeed, Muhammed; Sahebkar, Amirhossein

    2017-02-10

    Curcumin, a bioactive polyphenol, is a yellow pigment of the Curcuma longa (turmeric) plant. Curcumin has many pharmacologic effects including antioxidant, anti-carcinogenic, anti-obesity, anti-angiogenic and anti-inflammatory properties. Recently, it has been found that curcumin affects lipid metabolism, and subsequently, may alleviate hyperlipidemia and atherosclerosis. Plasma HDL cholesterol (HDL-C) is an independent negative risk predictor of cardiovascular disease (CVD). However, numerous clinical and genetic studies have yielded disappointing results about the therapeutic benefit of raising plasma HDL-C levels. Therefore, research efforts are now focused on improving HDL functionality, independent of HDL-C levels. The quality of HDL particles can vary considerably due to heterogeneity in composition. Consistent with its complexity in composition and metabolism, a wide range of biological activities is reported for HDL, including antioxidant, anti-glycation, anti-inflammatory, anti-thrombotic, anti-apoptotic and immune modulatory activities. Protective properties of curcumin may influence HDL functionality; therefore, we reviewed the literature to determine whether curcumin can augment HDL function. In this review, we concluded that curcumin may modulate markers of HDL function, such as apo-AI, CETP, LCAT, PON1, MPO activities and levels. Curcumin may subsequently improve conditions in which HDL is dysfunctional and may have potential as a therapeutic drug in future. Further clinical trials with bioavailability-improved formulations of curcumin are warranted to examine its effects on lipid metabolism and HDL function.

  16. The Nascent Development of Ecotourism in Lagong Hill

    OpenAIRE

    Ah-Choy Er

    2010-01-01

    Problem statement: The nascent development of ecotourism in Lagong Hill faces an interesting challenge. The aim of this research note is to evaluate the nascent development of ecotourism in Lagong Hill, Malaysia based on the common core precepts of ecotourism. Approach: The research methods comprise of secondary data collection and field survey via an in-depth interview with selected key informants. This is aided by on-field observation to verify and complement the re...

  17. Time to ditch HDL-C as a measure of HDL function?

    Science.gov (United States)

    Ronsein, Graziella E; Heinecke, Jay W

    2017-10-01

    Epidemiological and clinical studies link low levels of HDL cholesterol (HDL-C) with increased risk of atherosclerotic cardiovascular disease (CVD). However, genetic polymorphisms linked to HDL-C do not associate consistently with CVD risk, and randomized clinical studies of drugs that elevate HDL-C via different mechanisms failed to reduce CVD risk in statin-treated patients with established CVD. New metrics that capture HDL's proposed cardioprotective effects are therefore urgently needed. Recent studies demonstrate cholesterol efflux capacity (CEC) of serum HDL (serum depleted of cholesterol-rich atherogenic lipoproteins) is an independent and better predictor of incident and prevalent CVD risk than HDL-C. However, it remains unclear whether therapies that increase CEC are cardioprotective. Other key issues are the impact of HDL-targeted therapies on HDL particle size and concentration and the relationship of those changes to CEC and cardioprotection. It is time to end the clinical focus on HDL-C and to understand how HDL's function, protein composition and size contribute to CVD risk. It will also be important to link variations in function and size to HDL-targeted therapies. Developing new metrics for quantifying HDL function, based on better understanding HDL metabolism and macrophage CEC, is critical for achieving these goals.

  18. HDL-C Response Variability to Niacin ER in US Adults

    Directory of Open Access Journals (Sweden)

    Jennifer B. Christian

    2013-01-01

    Full Text Available Background. Niacin is the most effective treatment currently available for raising HDL-C levels. Objective. To evaluate if gender and baseline lipid levels have an effect on the HDL-C response of niacin ER and to identify factors that predict response to niacin ER at the 500 mg dose. Material and Methods. The change in HDL-C effect between baseline and follow-up levels was quantified in absolute change as well as dichotomized into high versus low response (high response was defined as an HDL-C effect of >15% increase and low response was HDL-C <5% in a sample of 834 individuals. Results. Both males and females with low HDL-C levels at baseline exhibited a response to treatment in the multivariate model (males, HDL-C <40 mg/dL: OR=5.18, 95% CI: 2.36–11.39; females, HDL-C <50 mg/dL: OR=5.40, 95% CI: 1.84–15.79. There was also a significant difference in the mean HDL-C effect between baseline and follow-up HDL-C levels in the 500 mg niacin ER dose group for both males (mean HDL-C effect = 0.08, P<0.001 and females (mean HDL-C effect = 0.10, P=0.019. Conclusion. Baseline HDL-C levels are the biggest predictor of response to niacin ER treatment for both males and females among the factors evaluated.

  19. Data in support of a central role of plasminogen activator inhibitor-2 polymorphism in recurrent cardiovascular disease risk in the setting of high HDL cholesterol and C-reactive protein using Bayesian network modeling.

    Science.gov (United States)

    Corsetti, James P; Salzman, Peter; Ryan, Dan; Moss, Arthur J; Zareba, Wojciech; Sparks, Charles E

    2016-09-01

    Data is presented that was utilized as the basis for Bayesian network modeling of influence pathways focusing on the central role of a polymorphism of plasminogen activator inhibitor-2 (PAI-2) on recurrent cardiovascular disease risk in patients with high levels of HDL cholesterol and C-reactive protein (CRP) as a marker of inflammation, "Influences on Plasminogen Activator Inhibitor-2 Polymorphism-Associated Recurrent Cardiovascular Disease Risk in Patients with High HDL Cholesterol and Inflammation" (Corsetti et al., 2016; [1]). The data consist of occurrence of recurrent coronary events in 166 post myocardial infarction patients along with 1. clinical data on gender, race, age, and body mass index; 2. blood level data on 17 biomarkers; and 3. genotype data on 53 presumptive CVD-related single nucleotide polymorphisms. Additionally, a flow diagram of the Bayesian modeling procedure is presented along with Bayesian network subgraphs (root nodes to outcome events) utilized as the data from which PAI-2 associated influence pathways were derived (Corsetti et al., 2016; [1]).

  20. High-density lipoprotein (HDL) metabolism and bone mass.

    Science.gov (United States)

    Papachristou, Nicholaos I; Blair, Harry C; Kypreos, Kyriakos E; Papachristou, Dionysios J

    2017-05-01

    It is well appreciated that high-density lipoprotein (HDL) and bone physiology and pathology are tightly linked. Studies, primarily in mouse models, have shown that dysfunctional and/or disturbed HDL can affect bone mass through many different ways. Specifically, reduced HDL levels have been associated with the development of an inflammatory microenvironment that affects the differentiation and function of osteoblasts. In addition, perturbation in metabolic pathways of HDL favors adipoblastic differentiation and restrains osteoblastic differentiation through, among others, the modification of specific bone-related chemokines and signaling cascades. Increased bone marrow adiposity also deteriorates bone osteoblastic function and thus bone synthesis, leading to reduced bone mass. In this review, we present the current knowledge and the future directions with regard to the HDL-bone mass connection. Unraveling the molecular phenomena that underline this connection will promote the deeper understanding of the pathophysiology of bone-related pathologies, such as osteoporosis or bone metastasis, and pave the way toward the development of novel and more effective therapies against these conditions. © 2017 Society for Endocrinology.

  1. HDL as a Target for Glycemic Control.

    Science.gov (United States)

    Waldman, Boris; Jenkins, Alicia J; Sullivan, David; Ng, Martin K C; Keech, Anthony C

    2017-01-01

    HDL has long been known for its role in reverse cholesterol transport, thought in part to explain the well-recognized links between low levels of HDL-C and cardiovascular disease. The past decade has seen increasing evidence from epidemiological, basic science and early human intervention studies that HDL biology is more complex and may influence the onset and progression of type 2 diabetes. Research has identified multiple potential pathways by which higher HDL particle concentrations or functional improvements may ameliorate the development and progression of the disease. These include promotion of insulin secretion and pancreatic islet beta-cell survival, promotion of peripheral glucose uptake, and suppression of inflammation. The relationships between HDL-C levels, commonly used in clinical practice, and HDL particle number, size and various HDL functions is complex, and is intimately linked with triglyceride metabolism. The complexity of these relationships is amplified in diabetes, which negatively impacts multiple aspects of lipoprotein biology. This article reviews the rationale for, and potential of, HDL-based anti-diabetic pharmacotherapy, with an emphasis on the particular challenges posed by diabetes-related HDL dysfunction, and on the difficulties of selecting appropriate targets and HDL-related biomarkers for research and for clinical practice. We discuss aspects of HDL metabolism that are known to be altered in type 2 diabetes, potentially useful measures of HDL-targeted therapy in diabetes, and review early intervention studies in humans. These areas provide a firm foundation for further research and knowledge expansion in this intriguing area of human health and disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Niacin Therapy, HDL Cholesterol, and Cardiovascular Disease: Is the HDL Hypothesis Defunct?

    Science.gov (United States)

    Mani, Preethi; Rohatgi, Anand

    2015-08-01

    High-density lipoprotein cholesterol (HDL-C) has been shown in epidemiologic studies to be associated with cardiovascular (CV) risk and thus significant efforts have been focused on HDL-C modulation. Multiple pharmaceutical agents have been developed with the goal of increasing HDL-C. Niacin, the most widely used medication to raise HDL-C, increases HDL-C by up to 25 % and was shown in multiple surrogate end point studies to reduce CV risk. However, two large randomized controlled trials of niacin, AIM-HIGH and HPS2-THRIVE, have shown that despite its effects on HDL-C, niacin does not decrease the incidence of CV events and may have significant adverse effects. Studies of other classes of agents such as cholesteryl ester transfer protein (CETP) inhibitors have also shown that even dramatic increases in HDL-C do not necessarily translate to reduction in clinical events. While these findings have cast doubt upon the importance of HDL-C modulation on CV risk, it is becoming increasingly clear that HDL function-related measures may be better targets for CV risk reduction. Increasing ApoA-I, the primary apolipoprotein associated with HDL, correlates with reduced risk of events, and HDL particle concentration (HDL-P) inversely associates with incident CV events adjusted for HDL-C and LDL particle measures. Cholesterol efflux, the mechanism by which macrophages in vessel walls secrete cholesterol outside cells, correlates with both surrogate end points and clinical events. The effects of niacin on these alternate measures of HDL have been conflicting. Further studies should determine if modulation of these HDL function markers translates to clinical benefits. Although the HDL cholesterol hypothesis may be defunct, the HDL function hypothesis is now poised to be rigorously tested.

  3. Seipin is required for converting nascent to mature lipid droplets

    Science.gov (United States)

    Wang, Huajin; Becuwe, Michel; Housden, Benjamin E; Chitraju, Chandramohan; Porras, Ashley J; Graham, Morven M; Liu, Xinran N; Thiam, Abdou Rachid; Savage, David B; Agarwal, Anil K; Garg, Abhimanyu; Olarte, Maria-Jesus; Lin, Qingqing; Fröhlich, Florian; Hannibal-Bach, Hans Kristian; Upadhyayula, Srigokul; Perrimon, Norbert; Kirchhausen, Tomas; Ejsing, Christer S; Walther, Tobias C; Farese, Robert V

    2016-01-01

    How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs. DOI: http://dx.doi.org/10.7554/eLife.16582.001 PMID:27564575

  4. Emerging therapeutic strategies to enhance HDL function

    Directory of Open Access Journals (Sweden)

    Urraca Concha

    2011-10-01

    Full Text Available Abstract Epidemiologic studies indicate a strong inverse correlation between plasma levels of high-density lipoproteins (HDL and cardiovascular disease (CVD. The most relevant cardioprotective mechanism mediated by HDL is thought to be reverse cholesterol transport (RCT. New insights in HDL biology and RCT have allowed the development of promising agents aimed to increase HDL function and promote atherosclerosis regression. In this regard, apo-AI analogs and CETP inhibitors dalcetrapib and anacetrapib have aroused a great interest and opened new expectations in the treatment of CVD.

  5. Dialysis Modalities and HDL Composition and Function.

    Science.gov (United States)

    Holzer, Michael; Schilcher, Gernot; Curcic, Sanja; Trieb, Markus; Ljubojevic, Senka; Stojakovic, Tatjana; Scharnagl, Hubert; Kopecky, Chantal M; Rosenkranz, Alexander R; Heinemann, Akos; Marsche, Gunther

    2015-09-01

    Lipid abnormalities may have an effect on clinical outcomes of patients on dialysis. Recent studies have indicated that HDL dysfunction is a hallmark of ESRD. In this study, we compared HDL composition and metrics of HDL functionality in patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) with those in healthy controls. We detected a marked suppression of several metrics of HDL functionality in patients on HD or PD. Compositional analysis revealed that HDL from both dialysis groups shifted toward a more proinflammatory phenotype with profound alterations in the lipid moiety and protein composition. With regard to function, cholesterol efflux and anti-inflammatory and antiapoptotic functions seemed to be more severely suppressed in patients on HD, whereas HDL-associated paraoxonase activity was lowest in patients on PD. Quantification of enzyme activities involved in HDL metabolism suggested that HDL particle maturation and remodeling are altered in patients on HD or PD. In summary, our study provides mechanistic insights into the formation of dysfunctional HDL in patients with ESRD who are on HD or PD.

  6. Dialysis Modalities and HDL Composition and Function

    Science.gov (United States)

    Holzer, Michael; Schilcher, Gernot; Curcic, Sanja; Trieb, Markus; Ljubojevic, Senka; Stojakovic, Tatjana; Scharnagl, Hubert; Kopecky, Chantal M.; Rosenkranz, Alexander R.; Heinemann, Akos

    2015-01-01

    Lipid abnormalities may have an effect on clinical outcomes of patients on dialysis. Recent studies have indicated that HDL dysfunction is a hallmark of ESRD. In this study, we compared HDL composition and metrics of HDL functionality in patients undergoing hemodialysis (HD) or peritoneal dialysis (PD) with those in healthy controls. We detected a marked suppression of several metrics of HDL functionality in patients on HD or PD. Compositional analysis revealed that HDL from both dialysis groups shifted toward a more proinflammatory phenotype with profound alterations in the lipid moiety and protein composition. With regard to function, cholesterol efflux and anti-inflammatory and antiapoptotic functions seemed to be more severely suppressed in patients on HD, whereas HDL-associated paraoxonase activity was lowest in patients on PD. Quantification of enzyme activities involved in HDL metabolism suggested that HDL particle maturation and remodeling are altered in patients on HD or PD. In summary, our study provides mechanistic insights into the formation of dysfunctional HDL in patients with ESRD who are on HD or PD. PMID:25745027

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

    Science.gov (United States)

    Rysz-Górzyńska, Magdalena; Banach, Maciej

    2016-08-01

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

  8. Lipoprotein hydrophobic core lipids are partially extruded to surface in smaller HDL: “Herniated” HDL, a common feature in diabetes

    Science.gov (United States)

    Amigó, Núria; Mallol, Roger; Heras, Mercedes; Martínez-Hervás, Sergio; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles; Plana, Núria; Yanes, Óscar; Masana, Lluís; Correig, Xavier

    2016-01-01

    Recent studies have shown that pharmacological increases in HDL cholesterol concentrations do not necessarily translate into clinical benefits for patients, raising concerns about its predictive value for cardiovascular events. Here we hypothesize that the size-modulated lipid distribution within HDL particles is compromised in metabolic disorders that have abnormal HDL particle sizes, such as type 2 diabetes mellitus (DM2). By using NMR spectroscopy combined with a biochemical volumetric model we determined the size and spatial lipid distribution of HDL subclasses in a cohort of 26 controls and 29 DM2 patients before and after two drug treatments, one with niacin plus laropiprant and another with fenofibrate as an add-on to simvastatin. We further characterized the HDL surface properties using atomic force microscopy and fluorescent probes to show an abnormal lipid distribution within smaller HDL particles, a subclass particularly enriched in the DM2 patients. The reduction in the size, force cholesterol esters and triglycerides to emerge from the HDL core to the surface, making the outer surface of HDL more hydrophobic. Interestingly, pharmacological interventions had no effect on this undesired configuration, which may explain the lack of clinical benefits in DM2 subjects. PMID:26778677

  9. Regulation of the nascent brain vascular network by neural progenitors.

    Science.gov (United States)

    Santhosh, Devi; Huang, Zhen

    2015-11-01

    Neural progenitors are central players in the development of the brain neural circuitry. They not only produce the diverse neuronal and glial cell types in the brain, but also guide their migration in this process. Recent evidence indicates that neural progenitors also play a critical role in the development of the brain vascular network. At an early stage, neural progenitors have been found to facilitate the ingression of blood vessels from outside the neural tube, through VEGF and canonical Wnt signaling. Subsequently, neural progenitors directly communicate with endothelial cells to stabilize nascent brain vessels, in part through down-regulating Wnt pathway activity. Furthermore, neural progenitors promote nascent brain vessel integrity, through integrin αvβ8-dependent TGFβ signaling. In this review, we will discuss the evidence for, as well as questions that remain, regarding these novel roles of neural progenitors and the underlying mechanisms in their regulation of the nascent brain vascular network.

  10. Quantification of HDL proteins, cardiac events, and mortality in patients with type 2 diabetes on hemodialysis.

    Science.gov (United States)

    Kopecky, Chantal; Genser, Bernd; Drechsler, Christiane; Krane, Vera; Kaltenecker, Christopher C; Hengstschläger, Markus; März, Winfried; Wanner, Christoph; Säemann, Marcus D; Weichhart, Thomas

    2015-02-06

    Impairment of HDL function has been associated with cardiovascular events in patients with kidney failure. The protein composition of HDLs is altered in these patients, presumably compromising the cardioprotective effects of HDLs. This post hoc study assessed the relation of distinct HDL-bound proteins with cardiovascular outcomes in a dialysis population. The concentrations of HDL-associated serum amyloid A (SAA) and surfactant protein B (SP-B) were measured in 1152 patients with type 2 diabetes mellitus on hemodialysis participating in The German Diabetes Dialysis Study who were randomly assigned to double-blind treatment of 20 mg atorvastatin daily or matching placebo. The association of SAA(HDL) and SP-B(HDL) with cardiovascular outcomes was assessed in multivariate regression models adjusted for known clinical risk factors. High concentrations of SAA(HDL) were significantly and positively associated with the risk of cardiac events (hazard ratio per 1 SD higher, 1.09; 95% confidence interval, 1.01 to 1.19). High concentrations of SP-B(HDL) were significantly associated with all-cause mortality (hazard ratio per 1 SD higher, 1.10; 95% confidence interval, 1.02 to 1.19). Adjustment for HDL cholesterol did not affect these associations. In patients with diabetes on hemodialysis, SAA(HDL) and SP-B(HDL) were related to cardiac events and all-cause mortality, respectively, and they were independent of HDL cholesterol. These findings indicate that a remodeling of the HDL proteome was associated with a higher risk for cardiovascular events and mortality in patients with ESRD. Copyright © 2015 by the American Society of Nephrology.

  11. A Possible Role of the Full-Length Nascent Protein in Post-Translational Ribosome Recycling

    Science.gov (United States)

    Das, Debasis; Samanta, Dibyendu; Bhattacharya, Arpita; Basu, Arunima; Das, Anindita; Ghosh, Jaydip; Chakrabarti, Abhijit; Das Gupta, Chanchal

    2017-01-01

    Each cycle of translation initiation in bacterial cell requires free 50S and 30S ribosomal subunits originating from the post-translational dissociation of 70S ribosome from the previous cycle. Literature shows stable dissociation of 70S from model post-termination complexes by the concerted action of Ribosome Recycling Factor (RRF) and Elongation Factor G (EF-G) that interact with the rRNA bridge B2a/B2b joining 50S to 30S. In such experimental models, the role of full-length nascent protein was never considered seriously. We observed relatively slow release of full-length nascent protein from 50Sof post translation ribosome, and in that process, its toe prints on the rRNA in vivo and in in vitro translation with E.coli S30 extract. We reported earlier that a number of chemically unfolded proteins like bovine carbonic anhydrase (BCA), lactate dehydrogenase (LDH), malate dehydrogenase (MDH), lysozyme, ovalbumin etc., when added to free 70Sin lieu of the full length nascent proteins, also interact with identical RNA regions of the 23S rRNA. Interestingly the rRNA nucleotides that slow down release of the C-terminus of full-length unfolded protein were found in close proximity to the B2a/B2b bridge. It indicated a potentially important chemical reaction conserved throughout the evolution. Here we set out to probe that conserved role of unfolded protein conformation in splitting the free or post-termination 70S. How both the RRF-EFG dependent and the plausible nascent protein–EFG dependent ribosome recycling pathways might be relevant in bacteria is discussed here. PMID:28099529

  12. Entry and Exit Dynamics of Nascent Business Owners

    DEFF Research Database (Denmark)

    Rocha, Vera; Carneiro, Anabela; Varum, Celeste

    2015-01-01

    in the labor market and entry modes shape the post-entry dynamics of nascent business owners. By differentiating between different entry and exit routes, this paper provides new evidence on different human capital patterns among nascent business owners and on key determinants of entrepreneurial survival. Our...... results suggest that different exit modes can be predicted by business owners’ entry route. Furthermore, different exit modes exhibit different duration dependence patterns according to the entry mode. Additionally, the paper shows that businesses started after a displacement episode are not necessarily...

  13. Metabolic and functional relevance of HDL subspecies

    Science.gov (United States)

    Though the association of high-density lipoprotein cholesterol (HDL-C) with cardiovascular disease (CVD) was described as early as 1950, HDL’s role in CVD still remains to be fully elucidated. There are numerous publications showing the inverse relationship between HDL-C and CVD risk; however, in t...

  14. Niacin to Boost Your HDL "Good" Cholesterol

    Science.gov (United States)

    Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

  15. Conserved C-terminal nascent peptide binding domain of HYPK facilitates its chaperone-like activity

    Indian Academy of Sciences (India)

    Swasti Raychaudhuri; Rachana Banerjee; Subhasish Mukhopadhyay; Nitai P Bhattacharyya

    2014-09-01

    Human HYPK (Huntingtin Yeast-two-hybrid Protein K) is an intrinsically unstructured chaperone-like protein with no sequence homology to known chaperones. HYPK is also known to be a part of ribosome-associated protein complex and present in polysomes. The objective of the present study was to investigate the evolutionary influence on HYPK primary structure and its impact on the protein’s function. Amino acid sequence analysis revealed 105 orthologs of human HYPK from plants, lower invertebrates to mammals. C-terminal part of HYPK was found to be particularly conserved and to contain nascent polypeptide-associated alpha subunit (NPAA) domain. This region experiences highest selection pressure, signifying its importance in the structural and functional evolution. NPAA domain of human HYPK has unique amino acid composition preferring glutamic acid and happens to be more stable from a conformational point of view having higher content of -helices than the rest. Cell biology studies indicate that overexpressed C-terminal human HYPK can interact with nascent proteins, co-localizes with huntingtin, increases cell viability and decreases caspase activities in Huntington’s disease (HD) cell culture model. This domain is found to be required for the chaperone-like activity of HYPK in vivo. Our study suggested that by virtue of its flexibility and nascent peptide binding activity, HYPK may play an important role in assisting protein (re)folding.

  16. High density lipoprotein (HDL) metabolism in noninsulin-dependent diabetes mellitus: measurement of HDL turnover using tritiated HDL

    Energy Technology Data Exchange (ETDEWEB)

    Golay, A.; Zech, L.; Shi, M.Z.; Chiou, Y.A.; Reaven, G.M.; Chen, Y.D.

    1987-09-01

    High density lipoprotein (HDL) kinetics were studied by injecting (/sup 3/H)apoprotein A-I (apoA-I)/HDL into 12 subjects with normal glucose tolerance and 12 patients with noninsulin-dependent diabetes mellitus (NIDDM). The results indicate that the mean fractional catabolic rate (FCR) of apoA-I/HDL was significantly faster (0.63 +/- 0.07 (+/- SEM) vs. 0.39 +/- 0.02 1/day; P less than 0.001) and the apoA-I/HDL synthetic rate greater (29.4 +/- 2.9 vs. 22.9 +/- 1.3 mg/kg X day; P less than 0.02) in patients with NIDDM than in normal subjects. Furthermore, there were statistically significant inverse relationships between apoA-I/HDL FCR and plasma levels of both HDL cholesterol (r = -0.71; P less than 0.001) and apoA-I (r = -0.63; P less than 0.001). In addition, the increase in apoA-I/HDL FCR was directly related to fasting plasma glucose (r = 0.78; P less than 0.001) and insulin (r = 0.76; P less than 0.001) concentrations. These data support the view that the decrease in plasma HDL cholesterol and apoA-I levels commonly found in patients with noninsulin-dependent diabetes is due to an increase in the catabolic rate of apoA-I/HDL secondary to the defects in carbohydrate metabolism present in these patients.

  17. Entrepreneurial Identity and Role Expectations in Nascent Entrepreneurship

    Science.gov (United States)

    Lundqvist, Mats; Middleton, Karen Williams; Nowell, Pamela

    2015-01-01

    Entrepreneurship has been defined as an individual?new value creation dialogic. To study how entrepreneurial identity evolves, this article, drawing on entrepreneurial learning theory, adds an entrepreneurial role expectations dialogic. Longitudinal evidence from nascent entrepreneurs working in venture teams on invention disclosures offers an…

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

    Directory of Open Access Journals (Sweden)

    Xiang Ji

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

  19. Anion Exchange HPLC Isolation of High-Density Lipoprotein (HDL) and On-Line Estimation of Proinflammatory HDL

    Science.gov (United States)

    Ji, Xiang; Xu, Hao; Zhang, Hao; Hillery, Cheryl A.; Gao, Hai-qing; Pritchard, Kirkwood A.

    2014-01-01

    Proinflammatory high-density lipoprotein (p-HDL) is a biomarker of cardiovascular disease. Sickle cell disease (SCD) is characterized by chronic states of oxidative stress that many consider to play a role in forming p-HDL. To measure p-HDL, apolipoprotein (apo) B containing lipoproteins are precipitated. Supernatant HDL is incubated with an oxidant/LDL or an oxidant alone and rates of HDL oxidation monitored with dichlorofluorescein (DCFH). Although apoB precipitation is convenient for isolating HDL, the resulting supernatant matrix likely influences HDL oxidation. To determine effects of supernatants on p-HDL measurements we purified HDL from plasma from SCD subjects by anion exchange (AE) chromatography, determined its rate of oxidation relative to supernatant HDL. SCD decreased total cholesterol but not triglycerides or HDL and increased cell-free (cf) hemoglobin (Hb) and xanthine oxidase (XO). HDL isolated by AE-HPLC had lower p-HDL levels than HDL in supernatants after apoB precipitation. XO+xanthine (X) and cf Hb accelerated purified HDL oxidation. Although the plate and AE-HPLC assays both showed p-HDL directly correlated with cf-Hb in SCD plasma, the plate assay yielded p-HDL data that was influenced more by cf-Hb than AE-HPLC generated p-HDL data. The AE-HPLC p-HDL assay reduces the influence of the supernatants and shows that SCD increases p-HDL. PMID:24609013

  20. Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

    National Research Council Canada - National Science Library

    Smart, Eric J; Li, Xiang-An; Liu, Jun; Swanson, Hollie; Post, Steven; Guerin, Theresa; Ballard, Hubert O; White, James; Everson, William V; Zhu, Haining; Graf, Gregory A; Gong, Ming; Ross, Stuart A

    2008-01-01

    .... Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls...

  1. Diabetic HDL-associated myristic acid inhibits acetyicholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin

    National Research Council Canada - National Science Library

    James White; Theresa Guerin; Hollie Swanson; Steven Post; Haining Zhu; Ming Gong; Jun Liu; William V Everson; Xiang-An Li; Gregory A Graf; Hubert O Ballard; Stuart A Ross; Eric J Smart

    2008-01-01

    .... Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls...

  2. Significant abnormalities of the HDL phosphosphingolipidome in type 1 diabetes despite normal HDL cholesterol concentration.

    Science.gov (United States)

    Denimal, Damien; Pais de Barros, Jean-Paul; Petit, Jean-Michel; Bouillet, Benjamin; Vergès, Bruno; Duvillard, Laurence

    2015-08-01

    Phospholipids and sphingolipids are major components of HDL. They play a critical role in HDL functionality and protective effects against atherosclerosis. As HDL are dysfunctional in type 1 diabetic patients, we ascertained whether they presented abnormalities in their phospholipid and sphingolipid profile, despite normal HDL cholesterol concentration. Using liquid chromatography-tandem mass spectrometry, we quantified the main species of phosphatidylcholines, sphingomyelins, lysophophatidylcholines, phosphatidylethanolamines, phosphatidylinositols, ceramides, plasmalogens and sphingosines 1-phosphate in the HDL2 and HDL3 from 54 type 1 diabetic patients and 50 controls. Serum HDL cholesterol was similar in the 2 groups of subjects. When data were expressed relative to the total amount of phospholipids and sphingolipids, sphingosines-1-phosphate (S1P) were 11.7% (NS) and 14.4% (p = 0.0062) lower in HDL2 and HDL3, respectively, from type 1 diabetic patients than from controls. Ceramides were 23% (p = 0.005) and 24% (borderline significance) lower in HDL2 and HDL3, respectively. The concentration of apolipoprotein M, the carrier of S1P, was similar in patients and controls. In type 1 diabetic patients compared to controls, the concentration of d18:1-S1P, the main S1P species, was decreased in total plasma (-17.0%, p HDL fraction (-21.9%, p HDL fraction (-13.7%, p = 0.012). The concentration of ceramides was decreased in total plasma (-24.4%, p HDL fraction (-27.9%, p = 0.0006) and non-HDL fraction (-22.0%, p = 0.0087). Despite normal HDL cholesterol level, the phospholipid + sphingolipid profile is impaired in HDL from type 1 diabetic patients. These abnormalities, especially the decrease in S1P, could contribute to the impaired HDL functionality observed in these patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  3. Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits.

    Science.gov (United States)

    López-Olmos, Victoria; Carreón-Torres, Elizabeth; Luna-Luna, María; Flores-Castillo, Cristobal; Martínez-Ramírez, Miriam; Bautista-Pérez, Rocío; Franco, Martha; Sandoval-Zárate, Julio; Roldán, Francisco-Javier; Aranda-Fraustro, Alberto; Soria-Castro, Elizabeth; Muñoz-Vega, Mónica; Fragoso, José-Manuel; Vargas-Alarcón, Gilberto; Pérez-Méndez, Oscar

    2016-03-01

    The catabolism and structure of high-density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A-I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL-apo A-I was evaluated by exogenous radiolabelling with iodine-131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol-to-phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [(131)I]-apo A-I in the proteinuric rabbits was faster (FCR = 0.036 h(-1)) compared to control rabbits group (FCR = 0.026 h(-1), P HDL, whereas PON-1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase-1 activity, and a rise in the fractional catabolic rate of the [(131)I]-apo A-I.

  4. HDL particle number and size as predictors of cardiovascular disease.

    Science.gov (United States)

    Kontush, Anatol

    2015-01-01

    Previous studies indicate that reduced concentrations of circulating high-density lipoprotein (HDL) particles can be superior to HDL-cholesterol (HDL-C) levels as a predictor of cardiovascular disease. Measurements of HDL particle numbers, therefore, bear a potential for the improved assessment of cardiovascular risk. Furthermore, such measurement can be relevant for the evaluation of novel therapeutic approaches targeting HDL. Modern in-depth analyses of HDL particle profile may further improve evaluation of cardiovascular risk. Although clinical relevance of circulating concentrations of HDL subpopulations to cardiovascular disease remains controversial, the negative relationship between the number of large HDL particles and cardiovascular disease suggests that assessment of HDL particle profile can be clinically useful. Reduced mean HDL size is equally associated with cardiovascular disease in large-scale clinical studies. Since HDL-C is primarily carried in the circulation by large, lipid-rich HDL particles, the inverse relationship between HDL size and cardiovascular risk can be secondary to those established for plasma levels of HDL particles, HDL-C, and large HDL. The epidemiological data thereby suggest that HDL particle number may represent a more relevant therapeutic target as compared to HDL-C.

  5. A High Throughput Biochemical Fluorometric Method for Measuring Lipid Peroxidation in HDL

    Science.gov (United States)

    Kelesidis, Theodoros; Roberts, Christian K.; Huynh, Diana; Martínez-Maza, Otoniel; Currier, Judith S.; Reddy, Srinivasa T.; Yang, Otto O.

    2014-01-01

    Current cell-based assays for determining the functional properties of high-density lipoproteins (HDL) have limitations. We report here the development of a new, robust fluorometric cell-free biochemical assay that measures HDL lipid peroxidation (HDLox) based on the oxidation of the fluorochrome Amplex Red. HDLox correlated with previously validated cell-based (r = 0.47, pHDL in established animal models of atherosclerosis and Human Immunodeficiency Virus (HIV) patients. Using an immunoaffinity method for capturing HDL, we demonstrate the utility of this novel assay for measuring HDLox in a high throughput format. Furthermore, HDLox correlated significantly with measures of cardiovascular diseases including carotid intima media thickness (r = 0.35, pHDL function/quality that is suitable for high throughput implementation. PMID:25368900

  6. Decreased high-density lipoprotein (HDL) particle size, prebeta-, and large HDL subspecies concentration in Finnish low-HDL families: relationship with intima-media thickness.

    Science.gov (United States)

    Watanabe, Hiroshi; Söderlund, Sanni; Soro-Paavonen, Aino; Hiukka, Anne; Leinonen, Eeva; Alagona, Corradina; Salonen, Riitta; Tuomainen, Tomi-Pekka; Ehnholm, Christian; Jauhiainen, Matti; Taskinen, Marja-Riitta

    2006-04-01

    High-density lipoprotein (HDL) cholesterol correlates inversely with the risk of coronary heart disease (CHD). The precise antiatherogenic mechanisms of HDL subspecies are not thoroughly elucidated. We studied the relationship between carotid intima-media thickness (IMT) and HDL subspecies distribution in Finnish families with low HDL cholesterol and premature CHD. Altogether, 148 members of Finnish low-HDL families and 133 healthy control subjects participated in our study. HDL particle size was significantly smaller in affected family members (HDL family members and control subjects (9.1+/-0.04 nm versus 9.5+/-0.05 nm, Pfamily members. Mean IMT was significantly higher in the affected family members than in the control subjects (0.85+/-0.01 mm versus 0.79+/-0.01 mm; Ppressure, and prebeta-HDL were significant independent determinants of mean IMT. The decreased levels of HDL2b and prebeta-HDL reflect the potentially efflux-deficient HDL subspecies profile in the affected low-HDL family members. Decreased HDL particle size caused by the decrease of plasma concentration of HDL2b and decreased prebeta-HDL levels correlate with increased IMT.

  7. Transcription arrest caused by long nascent RNA chains

    DEFF Research Database (Denmark)

    Bentin, Thomas; Cherny, Dmitry; Larsen, H Jakob

    2004-01-01

    the number of active elongation complexes. Thus transcription behaved as an all-or-none process. The mechanism of transcription inhibition was explored using electron microscopy and further biochemical experiments. The data suggest that multiple mechanisms may contribute to the observed effects. Part......The transcription process is highly processive. However, specific sequence elements encoded in the nascent RNA may signal transcription pausing and/or termination. We find that under certain conditions nascent RNA chains can have a strong and apparently sequence-independent inhibitory effect...... on transcription. Using phage T3 RNA polymerase (T3 RNAP) and covalently closed circular (cccDNA) DNA templates that did not contain any strong termination signal, transcription was severely inhibited after a short period of time. Less than approximately 10% residual transcriptional activity remained after 10 min...

  8. Evaluation of HDL-modulating interventions for cardiovascular risk reduction using a systems pharmacology approach[S

    Science.gov (United States)

    Gadkar, Kapil; Lu, James; Sahasranaman, Srikumar; Davis, John; Mazer, Norman A.; Ramanujan, Saroja

    2016-01-01

    The recent failures of cholesteryl ester transport protein inhibitor drugs to decrease CVD risk, despite raising HDL cholesterol (HDL-C) levels, suggest that pharmacologic increases in HDL-C may not always reflect elevations in reverse cholesterol transport (RCT), the process by which HDL is believed to exert its beneficial effects. HDL-modulating therapies can affect HDL properties beyond total HDL-C, including particle numbers, size, and composition, and may contribute differently to RCT and CVD risk. The lack of validated easily measurable pharmacodynamic markers to link drug effects to RCT, and ultimately to CVD risk, complicates target and compound selection and evaluation. In this work, we use a systems pharmacology model to contextualize the roles of different HDL targets in cholesterol metabolism and provide quantitative links between HDL-related measurements and the associated changes in RCT rate to support target and compound evaluation in drug development. By quantifying the amount of cholesterol removed from the periphery over the short-term, our simulations show the potential for infused HDL to treat acute CVD. For the primary prevention of CVD, our analysis suggests that the induction of ApoA-I synthesis may be a more viable approach, due to the long-term increase in RCT rate. PMID:26522778

  9. In situ AFM imaging of apolipoprotein A-I directly derived from plasma HDL.

    Science.gov (United States)

    Gan, Chaoye; Wang, Zhexuan; Chen, Yong

    2017-04-01

    The major apolipoproteins of plasma lipoproteins play vital roles in the structural integrity and physiological functions of lipoproteins. More than ten structural models of apolipoprotein A-I (apoA-I), the major apolipoprotein of high-density lipoprotein (HDL), have been developed successively. In these models, apoA-I was supposed to organize in a ring-shaped form. To date, however, there is no direct evidence under physiological condition. Here, atomic force microscopy (AFM) was used to in situ visualize the organization of apoA-I, which was exposed via depletion of the lipid component of plasma HDL pre-immobilized on functionalized mica sheets. For the first time, the ring-shaped coarse structure and three detailed structures (crescent-shaped, gapped "O"-shaped, and parentheses-shaped structures, respectively) of apoA-I in plasma HDL, which have the ability of binding scavenger receptors, were directly observed and quantitatively measured by AFM. The three detailed structures probably represent the different extents to which the lipid component of HDL was depleted. Data on lipid depletion of HDL may provide clues to understand lipid insertion of HDL. These data provide important information for the understanding of the structure/maturation of plasma HDL. Moreover, they suggest a powerful method for directly visualizing the major apolipoproteins of plasma lipoproteins or the protein component of lipoprotein-like lipid-protein complexes. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Beyond the genetics of HDL : why is HDL cholesterol inversely related to cardiovascular disease?

    NARCIS (Netherlands)

    Kuivenhoven, J A; Groen, A K

    2015-01-01

    There is unequivocal evidence that high-density lipoprotein (HDL) cholesterol levels in plasma are inversely associated with the risk of cardiovascular disease (CVD). Studies of families with inherited HDL disorders and genetic association studies in general (and patient) population samples have ide

  11. Beyond the genetics of HDL : why is HDL cholesterol inversely related to cardiovascular disease?

    NARCIS (Netherlands)

    Kuivenhoven, J A; Groen, A K

    2015-01-01

    There is unequivocal evidence that high-density lipoprotein (HDL) cholesterol levels in plasma are inversely associated with the risk of cardiovascular disease (CVD). Studies of families with inherited HDL disorders and genetic association studies in general (and patient) population samples have

  12. Scavenger receptor B1 (SR-B1) profoundly excludes high density lipoprotein (HDL) apolipoprotein AII as it nibbles HDL-cholesteryl ester.

    Science.gov (United States)

    Gillard, Baiba K; Bassett, G Randall; Gotto, Antonio M; Rosales, Corina; Pownall, Henry J

    2017-05-26

    Reverse cholesterol transport (transfer of macrophage-cholesterol in the subendothelial space of the arterial wall to the liver) is terminated by selective high density lipoprotein (HDL)-cholesteryl ester (CE) uptake, mediated by scavenger receptor class B, type 1 (SR-B1). We tested the validity of two models for this process: "gobbling," i.e. one-step transfer of all HDL-CE to the cell and "nibbling," multiple successive cycles of SR-B1-HDL association during which a few CEs transfer to the cell. Concurrently, we compared cellular uptake of apoAI with that of apoAII, which is more lipophilic than apoAI, using HDL-[(3)H]CE labeled with [(125)I]apoAI or [(125)I]apoAII. The studies were conducted in CHO-K1 and CHO-ldlA7 cells (LDLR(-/-)) with (CHO-SR-B1) and without SR-B1 overexpression and in human Huh7 hepatocytes. Relative to CE, both apoAI and apoAII were excluded from uptake by all cells. However, apoAII was more highly excluded from uptake (2-4×) than apoAI. To distinguish gobbling versus nibbling mechanisms, media from incubations of HDL with CHO-SR-B1 cells were analyzed by non-denaturing PAGE, size-exclusion chromatography, and the distribution of apoAI, apoAII, cholesterol, and phospholipid among HDL species as a function of incubation time. HDL size gradually decreased, i.e. nibbling, with the concurrent release of lipid-free apoAI; apoAII was retained in an HDL remnant. Our data support an SR-B1 nibbling mechanism that is similar to that of streptococcal serum opacity factor, which also selectively removes CE and releases apoAI, leaving an apoAII-rich remnant. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Evidence of linkage of HDL level variation to APOC3 in two samples with different ascertainment.

    Science.gov (United States)

    Gagnon, France; Jarvik, Gail P; Motulsky, Arno G; Deeb, Samir S; Brunzell, John D; Wijsman, Ellen M

    2003-11-01

    The APOA1-C3-A4-A5 gene complex encodes genes whose products are implicated in the metabolism of HDL and/or triglycerides. Although the relationship between polymorphisms in this gene cluster and dyslipidemias was first reported more than 15 years ago, association and linkage results have remained inconclusive. This is due, in part, to the oligogenic and multivariate nature of dyslipidemic phenotypes. Therefore, we investigate evidence of linkage of APOC3 and HDL using two samples of dyslipidemic pedigrees: familial combined hyperlipidemia (FCHL) and isolated low-HDL (ILHDL). We used a strategy that deals with several difficulties inherent in the study of complex traits: by using a Bayesian Markov Chain Monte Carlo (MCMC) approach we allow for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. By using this approach on extended pedigrees we provide evidence of linkage of APOC3 and HDL level variation in two samples with different ascertainment. In addition to APOC3, we estimate that two to three genes, each with a substantial effect on total variance, are responsible for HDL variation in both data sets. We also provide evidence, using the FCHL data set, for a pleiotropic effect between HDL, HDL3 and triglycerides at the APOC3 locus.

  14. Diabetic HDL-associated myristic acid inhibits acetylcholine-induced nitric oxide generation by preventing the association of endothelial nitric oxide synthase with calmodulin.

    Science.gov (United States)

    White, James; Guerin, Theresa; Swanson, Hollie; Post, Steven; Zhu, Haining; Gong, Ming; Liu, Jun; Everson, William V; Li, Xiang-An; Graf, Gregory A; Ballard, Hubert O; Ross, Stuart A; Smart, Eric J

    2008-01-01

    In the current study, we examined whether diabetes affected the ability of HDL to stimulate nitric oxide (NO) production. Using HDL isolated from both diabetic humans and diabetic mouse models, we found that female HDL no longer induced NO synthesis, despite containing equivalent amounts of estrogen as nondiabetic controls. Furthermore, HDL isolated from diabetic females and males prevented acetylcholine-induced stimulation of NO generation. Analyses of both the human and mouse diabetic HDL particles showed that the HDLs contained increased levels of myristic acid. To determine whether myristic acid associated with HDL particles was responsible for the decrease in NO generation, myristic acid was added to HDL isolated from nondiabetic humans and mice. Myristic acid-associated HDL inhibited the generation of NO in a dose-dependent manner. Importantly, diabetic HDL did not alter the levels of endothelial NO synthase or acetylcholine receptors associated with the cells. Surprisingly, diabetic HDL inhibited ionomycin-induced stimulation of NO production without affecting ionomycin-induced increases in intracellular calcium. Further analysis indicated that diabetic HDL prevented calmodulin from interacting with endothelial NO synthase (eNOS) but did not affect the activation of calmodulin kinase or calcium-independent mechanisms for stimulating eNOS. These studies are the first to show that a specific fatty acid associated with HDL inhibits the stimulation of NO generation. These findings have important implications regarding cardiovascular disease in diabetic patients.

  15. Triglyceride to HDL-C Ratio is Associated with Insulin Resistance in Overweight and Obese Children.

    Science.gov (United States)

    Iwani, Nur Ahmad Kamil Zati; Jalaludin, Muhammad Yazid; Zin, Ruziana Mona Wan Mohd; Fuziah, Md Zain; Hong, Janet Yeow Hua; Abqariyah, Yahya; Mokhtar, Abdul Halim; Wan Nazaimoon, Wan Mohamud

    2017-01-06

    The purpose of this study was to investigate the usefulness of triglyceride to hdl-c ratio (TG:HDL-C) as an insulin resistance (IR) marker for overweight and obese children. A total of 271 blood samples of obese and overweight children aged 9-16 years were analysed for fasting glucose, lipids and insulin. Children were divided into IR and non-insulin resistance, using homeostasis model assessment (HOMA). The children were then stratified by tertiles of TG: HDL-C ratio. The strength between TG:HDL-C ratio and other parameters of IR were quantified using Pearson correlation coefficient (r). Odds ratio was estimated using multiple logistic regression adjusted for age, gender, pubertal stages and IR potential risk factors. Children with IR had significantly higher TG:HDL-C ratio (2.48) (p = 0.01). TG:HDL-C ratio was significantly correlated with HOMA-IR (r = 0.104, p HDL-C ratio showed significant increase in mean insulin level (p = 0.03), HOMA-IR (p = 0.04) and significantly higher number of children with acanthosis nigricans and metabolic syndrome. The odds of having IR was about 2.5 times higher (OR = 2.47; 95% CI 1.23, 4.95; p = 0.01) for those in the highest tertiles of TG:HDL-C ratio. Hence, TG:HDL-C may be a useful tool to identify high risk individuals.

  16. Effects of diabetic HDL on endothelial cell function.

    Science.gov (United States)

    He, Dan; Pan, Bing; Ren, Hui; Zheng, Lemin

    2014-01-01

    Type 2 diabetes mellitus (T2DM) is accompanied by dysfunctional high-density lipoprotein (HDL) and this is characterized by alterations in its composition and structure compared with HDL from normal subjects (N-HDL). HDL from diabetic subjects (D-HDL) has a diminished endothelial protective capacity including reducted ability to exert antioxidative activity, stimulate endothelial cell (EC) production of nitric oxide (NO) and endothelium-dependent vasomotion, promote endothelial progenitor cell (EPC)-mediated endothelial repair. In addition, D-HDL promotes EC proliferation, migration and adhesion to the matrix. The present review provides an overview of these effects of diabetic HDL on EC function, as well as the possible changes of D-HDL structure and composition which may be responsible for the diminished endothelial protective capacity of D-HDL.

  17. Serum amyloid A impairs the antiinflammatory properties of HDL

    Science.gov (United States)

    Han, Chang Yeop; Tang, Chongren; Guevara, Myriam E.; Wei, Hao; Wietecha, Tomasz; Shao, Baohai; Subramanian, Savitha; Omer, Mohamed; Wang, Shari; O’Brien, Kevin D.; Marcovina, Santica M.; Wight, Thomas N.; Vaisar, Tomas; de Beer, Maria C.; de Beer, Frederick C.; Osborne, William R.; Elkon, Keith B.; Chait, Alan

    2015-01-01

    HDL from healthy humans and lean mice inhibits palmitate-induced adipocyte inflammation; however, the effect of the inflammatory state on the functional properties of HDL on adipocytes is unknown. Here, we found that HDL from mice injected with AgNO3 fails to inhibit palmitate-induced inflammation and reduces cholesterol efflux from 3T3-L1 adipocytes. Moreover, HDL isolated from obese mice with moderate inflammation and humans with systemic lupus erythematosus had similar effects. Since serum amyloid A (SAA) concentrations in HDL increase with inflammation, we investigated whether elevated SAA is a causal factor in HDL dysfunction. HDL from AgNO3-injected mice lacking Saa1.1 and Saa2.1 exhibited a partial restoration of antiinflammatory and cholesterol efflux properties in adipocytes. Conversely, incorporation of SAA into HDL preparations reduced antiinflammatory properties but not to the same extent as HDL from AgNO3-injected mice. SAA-enriched HDL colocalized with cell surface–associated extracellular matrix (ECM) of adipocytes, suggesting impaired access to the plasma membrane. Enzymatic digestion of proteoglycans in the ECM restored the ability of SAA-containing HDL to inhibit palmitate-induced inflammation and cholesterol efflux. Collectively, these findings indicate that inflammation results in a loss of the antiinflammatory properties of HDL on adipocytes, which appears to partially result from the SAA component of HDL binding to cell-surface proteoglycans, thereby preventing access of HDL to the plasma membrane. PMID:26642365

  18. HDL (Good), LDL (Bad) Cholesterol and Triglycerides

    Science.gov (United States)

    ... Thromboembolism Aortic Aneurysm More HDL (Good), LDL (Bad) Cholesterol and Triglycerides Updated:Jul 5,2017 Cholesterol isn’t just ... Your Cholesterol Score Explained What Are High Blood Cholesterol and Triglycerides? How Can I Improve My Cholesterol? | Spanish What ...

  19. Longitudinal study of alcohol consumption and HDL concentrations: a community-based study.

    Science.gov (United States)

    Huang, Shue; Li, Junjuan; Shearer, Gregory C; Lichtenstein, Alice H; Zheng, Xiaoming; Wu, Yuntao; Jin, Cheng; Wu, Shouling; Gao, Xiang

    2017-03-01

    Background: In cross-sectional studies and short-term clinical trials, it has been suggested that there is a positive dose-response relation between alcohol consumption and HDL concentrations. However, prospective data have been limited.Objective: We sought to determine the association between total alcohol intake, the type of alcohol-containing beverage, and the 6-y (2006-2012) longitudinal change in HDL-cholesterol concentrations in a community-based cohort.Design: A total of 71,379 Chinese adults (mean age: 50 y) who were free of cardiovascular diseases and cancer and did not use cholesterol-lowering agents during follow-up were included in the study. Alcohol intake was assessed via a questionnaire in 2006 (baseline), and participants were classified into the following categories of alcohol consumption: never, past, light (women: 0-0.4 servings/d; men: 0-0.9 servings/d), moderate (women: 0.5-1.0 servings/d; men: 1-2 servings/d), and heavy (women: >1.0 servings/d; men: >2 servings/d). HDL-cholesterol concentrations were measured in 2006, 2008, 2010, and 2012. We used generalized estimating equation models to examine the associations between baseline alcohol intake and the change in HDL-cholesterol concentrations with adjustment for age, sex, smoking, physical activity, obesity, hypertension, diabetes, liver function, and C-reactive protein concentrations.Results: An umbrella-shaped association was observed between total alcohol consumption and changes in HDL-cholesterol concentrations. Compared with never drinkers, past, light, moderate, and heavy drinkers experienced slower decreases in HDL cholesterol of 0.012 mmol · L(-1) · y(-1) (95% CI: 0.008, 0.016 mmol · L(-1) · y(-1)), 0.013 mmol · L(-1) · y(-1) (95% CI: 0.010, 0.016 mmol · L(-1) · y(-1)), 0.017 mmol · L(-1) · y(-1) (95% CI: 0.009, 0.025 mmol · L(-1) · y(-1)), and 0.008 mmol · L(-1) · y(-1) (95% CI: 0.005, 0.011 mmol · L(-1) · y(-1)), respectively (P HDL-cholesterol and triglyceride:HDL

  20. The Nascent Development of Ecotourism in Lagong Hill

    Directory of Open Access Journals (Sweden)

    Ah-Choy Er

    2010-01-01

    Full Text Available Problem statement: The nascent development of ecotourism in Lagong Hill faces an interesting challenge. The aim of this research note is to evaluate the nascent development of ecotourism in Lagong Hill, Malaysia based on the common core precepts of ecotourism. Approach: The research methods comprise of secondary data collection and field survey via an in-depth interview with selected key informants. This is aided by on-field observation to verify and complement the research findings. Results and Discussion: The ecotourism park management has exhibited environmentally responsible behavior. Nature conservation, tourism management, solid waste management and water utilization adopt the core precepts of ecosystem protection, minimal environmental impact and environmental education. However, there is a lack of outreach towards the indigenous people who are residing within this forest reserve. The Orang Asli, the indigenous people of this area, have profound and in-depth knowledge of the forest and its terrains. This local knowledge and cultural heritage has yet to be tapped as part of community-based ecotourism. In addition, there is a lack of scientific research on the impact of quarrying and timber production on ecotourism. Conclusion: The ecotourism venture in Lagong Hill fulfills the core precepts of ecotourism with the exception of the participation of indigenous people. There is a need to inculcate community-based ecotourism rather than primarily focusing on environmental or economic impacts. More scientific research is required to determine carrying capacity, and the impact of quarrying and timber production on ecotourism.

  1. Human carotid atherosclerotic plaque protein(s) change HDL protein(s) composition and impair HDL anti-oxidant activity.

    Science.gov (United States)

    Cohen, Elad; Aviram, Michael; Khatib, Soliman; Volkova, Nina; Vaya, Jacob

    2016-01-01

    High density lipoprotein (HDL) anti-atherogenic functions are closely associated with cardiovascular disease risk factor, and are dictated by its composition, which is often affected by environmental factors. The present study investigates the effects of the human carotid plaque constituents on HDL composition and biological functions. To this end, human carotid plaques were homogenized and incubated with HDL. Results showed that after incubation, most of the apolipoprotein A1 (Apo A1) protein was released from the HDL, and HDL diameter increased by an average of approximately 2 nm. In parallel, HDL antioxidant activity was impaired. In response to homogenate treatment HDL could not prevent the accelerated oxidation of LDL caused by the homogenate. Boiling of the homogenate prior to its incubation with HDL abolished its effects on HDL composition changes. Moreover, tryptophan fluorescence quenching assay revealed an interaction between plaque component(s) and HDL, an interaction that was reduced by 50% upon using pre-boiled homogenate. These results led to hypothesize that plaque protein(s) interacted with HDL-associated Apo A1 and altered the HDL composition. Immuno-precipitation of Apo A1 that was released from the HDL after its incubation with the homogenate revealed a co-precipitation of three isomers of actin. However, beta-actin alone did not significantly affect the HDL composition, and yet the active protein within the plaque was elusive. In conclusion then, protein(s) in the homogenate interact with HDL protein(s), leading to release of Apo A1 from the HDL particle, a process that was associated with an increase in HDL diameter and with impaired HDL anti-oxidant activity.

  2. Unraveling the complexities of the HDL lipidome1

    Science.gov (United States)

    Kontush, Anatol; Lhomme, Marie; Chapman, M. John

    2013-01-01

    Plasma high density lipoproteins (HDL) are small, dense, protein-rich particles compared with other lipoprotein classes; roughly half of total HDL mass is accounted for by lipid components. Phospholipids predominate in the HDL lipidome, accounting for 40–60% of total lipid, with lesser proportions of cholesteryl esters (30–40%), triglycerides (5–12%), and free cholesterol (5–10%). Lipidomic approaches have provided initial insights into the HDL lipidome with identification of over 200 individual molecular lipids species in normolipidemic HDL. Plasma HDL particles, however, reveal high levels of structural, compositional, and functional heterogeneity. Establishing direct relationships between HDL structure, composition, and atheroprotective functions bears the potential to identify clinically relevant HDL subpopulations. Furthermore, development of HDL-based therapies designed to target beneficial subspecies within the circulating HDL pool can be facilitated using this approach. HDL lipidomics can equally contribute to the identification of biomarkers of both normal and deficient HDL functionality, which may prove useful as biomarkers of cardiovascular risk. However, numerous technical issues remain to be addressed in order to make such developments possible. With all technical questions resolved, quantitative analysis of the molecular components of the HDL lipidome will contribute to expand our knowledge of cardiovascular and metabolic diseases. PMID:23543772

  3. High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol

    DEFF Research Database (Denmark)

    Sethi, Amar A; Sampson, Maureen; Warnick, Russell;

    2010-01-01

    We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.......We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors....

  4. High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol

    DEFF Research Database (Denmark)

    Sethi, Amar A; Sampson, Maureen; Warnick, Russell

    2010-01-01

    We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.......We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors....

  5. ApoCIII enrichment in HDL impairs HDL-mediated cholesterol efflux capacity.

    Science.gov (United States)

    Luo, Mengdie; Liu, Aiying; Wang, Shuai; Wang, Tianle; Hu, Die; Wu, Sha; Peng, Daoquan

    2017-05-24

    Apolipoprotein CIII (apoCIII) has been reported to be tightly associated with triglyceride metabolism and the susceptibility to coronary artery disease (CAD). Besides, apoCIII has also been found to affect the anti-apoptotic effects of HDL. However, the effect of apoCIII on HDL-mediated cholesterol efflux, the crucial function of HDL, has not been reported. A hospital-based case-control study was conducted to compare the apoCIII distribution in lipoproteins between CAD patients and nonCAD controls and to explore the relationship between HDL-associated apoCIII (apoCIIIHDL) and HDL-mediated cholesterol efflux. One hundred forty CAD patients and nighty nine nonCAD controls were included. Plasma apoCIII, apoCIIIHDL and cholesterol efflux capacity was measured. The apoCIIIHDL ratio (apoCIIIHDL over plasma apoCIII) was significantly higher in CAD patients than that in control group (0.52 ± 0.24 vs. 0.43 ± 0.22, P = 0.004). Both apoCIIIHDL and apoCIIIHDL ratio were inversely correlated with cholesterol efflux capacity (r = -0.241, P = 0.0002; r = -0.318, P HDL-mediated cholesterol efflux capacity (standardized β = -0.325, P HDL may affect HDL-mediated cholesterol efflux capacity, implying the alternative role of apoCIII in the atherogenesis.

  6. HDL in sepsis - risk factor and therapeutic approach.

    Science.gov (United States)

    Morin, Emily E; Guo, Ling; Schwendeman, Anna; Li, Xiang-An

    2015-01-01

    High-density lipoprotein (HDL) is a key component of circulating blood and plays essential roles in regulation of vascular endothelial function and immunity. Clinical data demonstrate that HDL levels drop by 40-70% in septic patients, which is associated with a poor prognosis. Experimental studies using Apolipoprotein A-I (ApoAI) null mice showed that HDL deficient mice are susceptible to septic death, and overexpressing ApoAI in mice to increase HDL levels protects against septic death. These clinical and animal studies support our hypothesis that a decrease in HDL level is a risk factor for sepsis, and raising circulating HDL levels may provide an efficient therapy for sepsis. In this review, we discuss the roles of HDL in sepsis and summarize the efforts of using synthetic HDL as a potential therapy for sepsis.

  7. HDL Cholesterol: How to Boost Your 'Good' Cholesterol

    Science.gov (United States)

    HDL cholesterol: How to boost your 'good' cholesterol Your cholesterol levels are an important measure of heart health. For HDL cholesterol, or "good" cholesterol, higher levels are better. By Mayo Clinic ...

  8. Relationship TG/HDL-C and insulin resistance in adult women by nutritional status

    Directory of Open Access Journals (Sweden)

    Lorena Belén

    2014-04-01

    Full Text Available Introduction: The ratio assessment TG/HDL-C is an indicator of LDL size, facilitating the detection of individuals with increased atherogenic risk. Estimating the size of the LDL becomes important, especially in patients with TG values near the upper limit of normal values of reference and HDL-C. The objective of the study is to estimate the association between TG/HDL-C and insulin resistance (IR by nutritional status in adult women attending the Foundation for Endocrine Metabolic Diseases Research and Applied Clinical Research (FIEEM.Material and methods: Design Cross-sectional, non-pregnant adult women, apparently healthy, older than 30 years old, attending FIEEM in the Autonomous City of Buenos Aires. Dependent variable: TG/HDL-C ≥ 3.0 considered high value. Independent variables: IR by homeostatic model index HOMA-IR ≥ 2.5 categorizing the sample into two groups: with and without IR, and controlled by nutritional status using body mass index (BMI and waist circumference (CC. SPSS Statistics 15.0, calculating X2 or Fisher exact test, OR with confidence intervals of 95% and establishing logistic regression p value < 0.05.Results: We evaluated a purposive sample of 104 women (31.4% and 26% IR with TG/HDL-C high. 84.6% were overweight or obese and 88.5% increased CC. Women with BMI had significantly increased 0.15-fold increased risk (95% CI = 0.01 to 1.26 for TG/HDL-C high (p = 0.04 than the control women. There was no significance with increased CC. The ratio TG/HDL-C high IR was significantly correlated (r = 0.30 p = 0.002.Conclusions: Body weight was significantly associated with IR and the ratio TG/HDL-C increased. This ratio correlated significantly with IR in apparently healthy women.

  9. Low HDL cholesterol and the risk of diabetic nephropathy and retinopathy: results of the ADVANCE study.

    Science.gov (United States)

    Morton, Jamie; Zoungas, Sophia; Li, Qiang; Patel, Anushka A; Chalmers, John; Woodward, Mark; Celermajer, David S; Beulens, Joline W J; Stolk, Ronald P; Glasziou, Paul; Ng, Martin K C

    2012-11-01

    Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes. A total of 11,140 patients with type 2 diabetes and at least one additional vascular risk factor were followed a median of 5 years. Cox proportional hazards models were used to assess the association between baseline HDL-C and the development of new or worsening microvascular disease, defined prospectively as a composite of renal and retinal events. The mean baseline HDL-C level was 1.3 mmol/L (SD 0.45 mmol/L [range 0.1-4.0]). During follow-up, 32% of patients developed new or worsening microvascular disease, with 28% experiencing a renal event and 6% a retinal event. Compared with patients in the highest third, those in the lowest third had a 17% higher risk of microvascular disease (adjusted hazard ratio 1.17 [95% CI 1.06-1.28], P = 0.001) after adjustment for potential confounders and regression dilution. This was driven by a 19% higher risk of renal events (1.19 [1.08-1.32], P = 0.0005). There was no association between thirds of HDL-C and retinal events (1.01 [0.82-1.25], P = 0.9). In patients with type 2 diabetes, HDL-C level is an independent risk factor for the development of microvascular disease affecting the kidney but not the retina.

  10. Organizational Knowledge Communication – a Nascent 3rd Order Disciplinarity

    DEFF Research Database (Denmark)

    Kastberg, Peter

    2014-01-01

    to Organizational Knowledge Communication, i.e., organization studies, communication theory and Knowledge Management, respectively. In their synthesis the three trajectories form a disciplinary triple helix, a triple helix which, in turn, gives rise to Organizational Knowledge Communication as a novel, 3rd order...... visible, becomes a disciplinarity. I theoretically present an example of such a punctual integration and point to some of the immediate research promises that it holds. This theoretical account ends by describing Organizational Knowledge Communication as a nascent 3rd order disciplinarity.......There is an emerging tendency that the organizational communication functions of larger companies enter into a symbiotic relationship with the companies’ Knowledge Management function. A tendency this journal has labelled Organizational Knowledge Communication. This should come as no surprise...

  11. A Proteomic Characterization of Factors Enriched at Nascent DNA Molecules

    Directory of Open Access Journals (Sweden)

    Andres J. Lopez-Contreras

    2013-04-01

    Full Text Available DNA replication is facilitated by multiple factors that concentrate in the vicinity of replication forks. Here, we developed an approach that combines the isolation of proteins on nascent DNA chains with mass spectrometry (iPOND-MS, allowing a comprehensive proteomic characterization of the human replisome and replisome-associated factors. In addition to known replisome components, we provide a broad list of proteins that reside in the vicinity of the replisome, some of which were not previously associated with replication. For instance, our data support a link between DNA replication and the Williams-Beuren syndrome and identify ZNF24 as a replication factor. In addition, we reveal that SUMOylation is widespread for factors that concentrate near replisomes, which contrasts with lower UQylation levels at these sites. This resource provides a panoramic view of the proteins that concentrate in the surroundings of the replisome, which should facilitate future investigations on DNA replication and genome maintenance.

  12. The opaque nascent starburst in NGC 1377: Spitzer SINGS observations

    CERN Document Server

    Roussel, H; Bendo, G J; Dale, D A; Draine, B T; Engelbracht, C W; Gordon, K D; Helou, G; Hollenbach, D J; Kennicutt, R C; Meyer, M J; Moustakas, J; Murphy, E J; Regan, M W; Rieke, G H; Sheth, K; Smith, J D; Spoon, H W; Walter, F

    2006-01-01

    We analyze extensive data on NGC1377 from the Spitzer Infrared Nearby Galaxies Survey (SINGS). Within the category of nascent starbursts, that we previously selected by their infrared to radio continuum ratios in large excess of the average and their hot dust, NGC1377 has the largest infrared excess yet measured. Optical imaging reveals a morphological distortion suggestive of a recent accretion event. Infrared spectroscopy reveals a compact and opaque source dominated by a hot, self-absorbed continuum (tau ~ 20 in the 10 micron silicate band). We provide physical evidence against non-stellar activity being the heating source. HII regions are detected through the single [NeII] line, probing 85% of ionizing photons are suppressed by dust. The only other detected emission features are molecular hydrogen lines, arguably excited mainly by shocks, besides photodissociation regions, and weak aromatic bands. The new observations support our interpretation in terms of an extremely young starburst (<1 Myr). More ge...

  13. HDL-Targeting Therapeutics: Past, Present and Future.

    Science.gov (United States)

    Zakiev, Emile; Feng, Ma; Sukhorukov, Vasily; Kontush, Anatol

    2017-01-01

    Large-scale epidemiological studies firmly established the association between low plasma levels of high-density lipoprotein-cholesterol (HDL-C) and elevated risk of cardiovascular disease. This relationship is thought to reflect the key biological function of HDL, which involves reverse cholesterol transport from the arterial wall to the liver for further excretion from the body. Other aspects of the cardioprotective HDL functionality include antioxidative, anti-inflammatory, anti-apoptotic, anti-thrombotic, vasodilatory, anti-infectious and antidiabetic activities. Over the last decades, wide interest in HDL as an athero- and cardioprotective particle has resulted in the development of HDL-C raising as a therapeutic approach to reduce cardiovascular risk. Several strategies to increase circulating HDL-C concentrations were developed that primarily included use of niacin and fibrates as potent HDL-C raising agents. In the statin era, inhibition of cholesteryl ester transfer protein, infusion of artificially reconstituted HDL and administration of apolipoprotein A-I mimetics were established as novel approaches to raise HDL-C. More recently, other strategies targeting HDL metabolism, such as upregulation of apolipoprotein A-I production by the liver, were added to the list of HDL therapeutics. This review summarises current knowledge of novel HDL-targeting therapies and discusses perspectives of their use. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Printed Circuit Board Design with HDL Designer

    Science.gov (United States)

    Winkert, Thomas K.; LaFourcade, Teresa

    2004-01-01

    Staying up to date with the latest CAD tools both from a cost and time perspective is difficult. Within a given organization there may be experts in Printed Circuit Board Design tools and experts in FPGA/VHDL tools. Wouldn't it be great to have someone familiar with HDL Designer be able to design PCBs without having to learn another tool? This paper describes a limited experiment to do this.

  15. [Therapeutic targets in the treatment of dyslipidemia: HDL and non-HDL cholesterol].

    Science.gov (United States)

    Brea Hernando, Ángel Julián

    2014-07-01

    Atherogenic dyslipidemia (AD) consists of the combination of an increase in very low density lipoproteins (VLDL), which results in increased plasma triglyceride (TG) levels, with a reduction of levels of high-density lipoprotein bound cholesterol (HDL-C), also accompanied by a high proportion of small and dense LDL particles. AD is considered the main cause of the residual risk of experiencing cardiovascular disease (CVD), which is still presented by any patient on treatment with statins despite maintaining low-density lipoprotein bound cholesterol (LDL-C) levels below the values considered to be the objective. Non-HDL cholesterol (non-HDL-c) reflects the number of atherogenic particles present in the plasma. This includes VLDL, intermediate density lipoproteins (IDL) and LDL. Non-HDL-c provides a better estimate of cardiovascular risk than LDL-c, especially in the presence of hypertriglyceridemia or AD. The European guidelines for managing dyslipidemia recommend that non-HDL-c values be less than 100 and 130 mg/dL for individuals with very high and high cardiovascular risk, respectively. However, these guidelines state that there is insufficient evidence to suggest that raising HDL-c levels incontrovertibly results in a reduction in CVD. Therefore, the guidelines do not set recommended HDL-c levels as a therapeutic objective. The guidelines, however, state that individuals with AD on treatment with statins could benefit from an additional reduction in their risk by using fibrates. Copyright © 2014 Sociedad Española de Arteriosclerosis y Elsevier España, S.L. All rights reserved.

  16. Genome scan for quantitative trait loci influencing HDL levels: evidence for multilocus inheritance in familial combined hyperlipidemia.

    Science.gov (United States)

    Gagnon, France; Jarvik, Gail P; Badzioch, Michael D; Motulsky, Arno G; Brunzell, John D; Wijsman, Ellen M

    2005-09-01

    Several genome scans in search of high-density lipoprotein (HDL) quantitative trait loci (QTLs) have been performed. However, to date the actual identification of genes implicated in the regulation of common forms of HDL abnormalities remains unsuccessful. This may be due, in part, to the oligogenic and multivariate nature of HDL regulation, and potentially, pleiotropy affecting HDL and other lipid-related traits. Using a Bayesian Markov Chain Monte Carlo (MCMC) approach, we recently provided evidence of linkage of HDL level variation to the APOA1-C3-A4-A5 gene complex, in familial combined hyperlipidemia pedigrees, with an estimated number of two to three large QTLs remaining to be identified. We also presented results consistent with pleiotropy affecting HDL and triglycerides at the APOA1-C3-A4-A5 gene complex. Here we use the same MCMC analytic strategy, which allows for oligogenic trait models, as well as simultaneous incorporation of covariates, in the context of multipoint analysis. We now present results from a genome scan in search for the additional HDL QTLs in these pedigrees. We provide evidence of linkage for additional HDL QTLs on chromosomes 3p14 and 13q32, with results on chromosome 3 further supported by maximum parametric and variance component LOD scores of 3.0 and 2.6, respectively. Weaker evidence of linkage was also obtained for 7q32, 12q12, 14q31-32 and 16q23-24.

  17. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally...... associated with type 2 diabetes is unknown. In a prospective study of the general population (n = 47,627), we tested whether HDL cholesterol-related genetic variants were associated with low HDL cholesterol levels and, in turn, with an increased risk of type 2 diabetes. HDL cholesterol-decreasing gene scores...... and allele numbers associated with up to -13 and -20% reductions in HDL cholesterol levels. The corresponding theoretically predicted hazard ratios for type 2 diabetes were 1.44 (95% CI 1.38-1.52) and 1.77 (1.61-1.95), whereas the genetic estimates were nonsignificant. Genetic risk ratios for type 2 diabetes...

  18. HDL dysfunction in diabetes: causes and possible treatments

    Science.gov (United States)

    Farbstein, Dan; Levy, Andrew P

    2012-01-01

    HDL is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. These functions include cholesterol efflux and reverse cholesterol transport, antioxidative and anti-inflammatory activities. However, HDL has been shown to undergo a loss of function in several pathophysiological states, as in the acute phase response, obesity and chronic inflammatory diseases. Some of these diseases were also shown to be associated with increased risk for cardiovascular disease. One such disease that is associated with HDL dysfunction and accelerated atherosclerosis is diabetes mellitus, a disease in which the HDL particle undergoes diverse structural modifications that result in significant changes in its function. This review will summarize the changes that occur in HDL in diabetes mellitus and how these changes lead to HDL dysfunction. Possible treatments for HDL dysfunction are also briefly described. PMID:22390807

  19. Digital design and verilog HDL fundamentals

    CERN Document Server

    Cavanagh, Joseph

    2011-01-01

    Comprehensive and self contained, this tutorial covers the design of a plethora of combinational and sequential logic circuits using conventional logic design and Verilog HDL. Number systems and number representations are presented along with various binary codes. Several advanced topics are covered, including functional decomposition and iterative networks. A variety of examples are provided for combinational and sequential logic, computer arithmetic, and advanced topics such as Hamming code error correction. Constructs supported by Verilog are described in detail. All designs are continued to completion. Each chapter includes numerous design issues of varying complexity to be resolved by the reader.

  20. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects.

    Science.gov (United States)

    Dullaart, Robin P F; Otvos, James D; James, Richard W

    2014-08-01

    We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabetes mellitus (T2DM). Serum PON-1 (arylesterase activity) and HDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 67 T2DM patients and in 56 non-diabetic subjects. PON-1 activity, HDL cholesterol and apoA-I were decreased in T2DM (all pHDL particle concentration was unaltered, but large HDL particles, medium HDL particles and HDL particle size were decreased, whereas small HDL particles were increased in T2DM (all pHDL cholesterol than to apoA-I (p=0.001). In turn, the positive relationship of PON-1 with the HDL particle concentration and with large HDL particles was stronger than that with HDL cholesterol (both pHDL cholesterol or HDL particle characteristics. PON-1 activity is more closely related to the HDL particle concentration or large HDL particles than to HDL cholesterol. Impaired PON-1 activity in T2DM is not to a considerable extent explained by altered HDL subfraction levels. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

  1. Genetic variants in ABCA1 promoter affect transcription activity and plasma HDL level in pigs.

    Science.gov (United States)

    Dang, Xiao-yong; Chu, Wei-wei; Shi, Heng-chuan; Yu, Shi-gang; Han, Hai-yin; Gu, Shu-Hua; Chen, Jie

    2015-01-25

    Excess accumulation of cholesterol in plasma may result in coronary artery disease. Numerous studies have demonstrated that ATP-binding cassette protein A1 (ABCA1) mediates the efflux of cholesterol and phospholipids to apolipoproteins, a process necessary for plasma high density lipoprotein (HDL) formation. Higher plasma levels of HDL are associated with lower risk for cardiovascular disease. Studies of human disease and animal models had shown that an increased hepatic ABCA1 activity relates to an enhanced plasma HDL level. In this study, we hypothesized that functional mutations in the ABCA1 promoter in pigs may affect gene transcription activity, and consequently the HDL level in plasma. The promoter region of ABCA1 was comparatively scanned by direct sequencing with pool DNA of high- and low-HDL groups (n=30 for each group). Two polymorphisms, c. - 608A>G and c. - 418T>A, were revealed with reverse allele distribution in the two groups. The two polymorphisms were completely linked and formed only G-A or A-T haplotypes when genotyped in a larger population (n=526). Furthermore, we found that the G-A/G-A genotype was associated with higher HDL and ABCA1 mRNA level than A-T/A-T genotype. Luciferase assay also revealed that G-A haplotype promoter had higher activity than A-T haplotype. Single-nucleotide mutant assay showed that c.-418T>A was the causal mutation for ABCA1 transcription activity alteration. Conclusively, we identified two completely linked SNPs in porcine ABCA1 promoter region which have influence on the plasma HDL level by altering ABCA1 gene transcriptional activity.

  2. Nicotinic Acid Accelerates HDL Cholesteryl Ester Turnover in Obese Insulin-Resistant Dogs.

    Directory of Open Access Journals (Sweden)

    Jérôme Le Bloc'h

    Full Text Available Nicotinic acid (NA treatment decreases plasma triglycerides and increases HDL cholesterol, but the mechanisms involved in these change are not fully understood. A reduction in cholesteryl ester transfer protein (CETP activity has been advanced to explain most lipid-modulating effects of NA. However, due to the central role of CETP in reverse cholesterol transport in humans, other effects of NA may have been hidden. As dogs have no CETP activity, we conducted this study to examine the specific effects of extended-release niacin (NA on lipids and high-density lipoprotein (HDL cholesteryl ester (CE turnover in obese Insulin-Resistant dogs with increase plasma triglycerides.HDL kinetics were assessed in fasting dogs before and four weeks after NA treatment through endogenous labeling of cholesterol and apolipoprotein AI by simultaneous infusion of [1,2 13C2] acetate and [5,5,5 2H3] leucine for 8 h. Kinetic data were analyzed by compartmental modeling. In vitro cell cholesterol efflux of serum from NA-treated dogs was also measured.NA reduced plasma total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, triglycerides (TG, and very-low-density lipoprotein TG concentrations (p < 0.05. The kinetic study also showed a higher cholesterol esterification rate (p < 0.05. HDL-CE turnover was accelerated (p < 0.05 via HDL removal through endocytosis and selective CE uptake (p < 0.05. We measured an elevated in vitro cell cholesterol efflux (p < 0.05 with NA treatment in accordance with a higher cholesterol esterification.NA decreased HDL cholesterol but promoted cholesterol efflux and esterification, leading to improved reverse cholesterol transport. These results highlight the CETP-independent effects of NA in changes of plasma lipid profile.

  3. HDL and glucose metabolism: current evidence and therapeutic potential.

    Science.gov (United States)

    Siebel, Andrew L; Heywood, Sarah Elizabeth; Kingwell, Bronwyn A

    2015-01-01

    High-density lipoprotein (HDL) and its principal apolipoprotein A-I (ApoA-I) have now been convincingly shown to influence glucose metabolism through multiple mechanisms. The key clinically relevant observations are that both acute HDL elevation via short-term reconstituted HDL (rHDL) infusion and chronically raising HDL via a cholesteryl ester transfer protein (CETP) inhibitor reduce blood glucose in individuals with type 2 diabetes mellitus (T2DM). HDL may mediate effects on glucose metabolism through actions in multiple organs (e.g., pancreas, skeletal muscle, heart, adipose, liver, brain) by three distinct mechanisms: (i) Insulin secretion from pancreatic beta cells, (ii) Insulin-independent glucose uptake, (iii) Insulin sensitivity. The molecular mechanisms appear to involve both direct HDL signaling actions as well as effects secondary to lipid removal from cells. The implications of glucoregulatory mechanisms linked to HDL extend from glycemic control to potential anti-ischemic actions via increased tissue glucose uptake and utilization. Such effects not only have implications for the prevention and management of diabetes, but also for ischemic vascular diseases including angina pectoris, intermittent claudication, cerebral ischemia and even some forms of dementia. This review will discuss the growing evidence for a role of HDL in glucose metabolism and outline related potential for HDL therapies.

  4. Neural Oscillations and a Nascent Corticohippocampal Theory of Reference.

    Science.gov (United States)

    Nieuwland, Mante S; Martin, Andrea E

    2017-01-27

    The ability to use words to refer to the world is vital to the communicative power of human language. In particular, the anaphoric use of words to refer to previously mentioned concepts (antecedents) allows dialogue to be coherent and meaningful. Psycholinguistic theory posits that anaphor comprehension involves reactivating a memory representation of the antecedent. Whereas this implies the involvement of recognition memory or the mnemonic subroutines by which people distinguish old from new, the neural processes for reference resolution are largely unknown. Here, we report time-frequency analysis of four EEG experiments to reveal the increased coupling of functional neural systems associated with referentially coherent expressions compared with referentially problematic expressions. Despite varying in modality, language, and type of referential expression, all experiments showed larger gamma-band power for referentially coherent expressions compared with referentially problematic expressions. Beamformer analysis in high-density Experiment 4 localized the gamma-band increase to posterior parietal cortex around 400-600 msec after anaphor onset and to frontal-temporal cortex around 500-1000 msec. We argue that the observed gamma-band power increases reflect successful referential binding and resolution, which links incoming information to antecedents through an interaction between the brain's recognition memory networks and frontal-temporal language network. We integrate these findings with previous results from patient and neuroimaging studies, and we outline a nascent corticohippocampal theory of reference.

  5. Nascent transcription affected by RNA polymerase IV in Zea mays.

    Science.gov (United States)

    Erhard, Karl F; Talbot, Joy-El R B; Deans, Natalie C; McClish, Allison E; Hollick, Jay B

    2015-04-01

    All eukaryotes use three DNA-dependent RNA polymerases (RNAPs) to create cellular RNAs from DNA templates. Plants have additional RNAPs related to Pol II, but their evolutionary role(s) remain largely unknown. Zea mays (maize) RNA polymerase D1 (RPD1), the largest subunit of RNA polymerase IV (Pol IV), is required for normal plant development, paramutation, transcriptional repression of certain transposable elements (TEs), and transcriptional regulation of specific alleles. Here, we define the nascent transcriptomes of rpd1 mutant and wild-type (WT) seedlings using global run-on sequencing (GRO-seq) to identify the broader targets of RPD1-based regulation. Comparisons of WT and rpd1 mutant GRO-seq profiles indicate that Pol IV globally affects transcription at both transcriptional start sites and immediately downstream of polyadenylation addition sites. We found no evidence of divergent transcription from gene promoters as seen in mammalian GRO-seq profiles. Statistical comparisons identify genes and TEs whose transcription is affected by RPD1. Most examples of significant increases in genic antisense transcription appear to be initiated by 3'-proximal long terminal repeat retrotransposons. These results indicate that maize Pol IV specifies Pol II-based transcriptional regulation for specific regions of the maize genome including genes having developmental significance.

  6. Scavenger receptor BI and HDL regulate thymocyte apoptosis in sepsis

    Science.gov (United States)

    Guo, Ling; Zheng, Zhong; Ai, Junting; Howatt, Deborah A.; Mittelstadt, Paul R.; Thacker, Seth; Daugherty, Alan; Ashwell, Jonathan D.; Remaley, Alan T.; Li, Xiang-An

    2014-01-01

    Objective Thymocyte apoptosis is a major event in sepsis; however, how this process is regulated remains poorly understood. Approach and Results Septic stress induces glucocorticoids (GC) production which triggers thymocyte apoptosis. Here, we used scavenger receptor BI (SR-BI) null mice, which are completely deficient in inducible GC (iGC) in sepsis, to investigate the regulation of thymocyte apoptosis in sepsis. Cecal ligation and puncture (CLP) induced profound thymocyte apoptosis in SR-BI+/+ mice, but no thymocyte apoptosis in SR-BI−/− mice due to lack of iGC. Unexpectedly, supplementation of GC only partly restored thymocyte apoptosis in SR-BI−/− mice. We demonstrated that HDL is a critical modulator for thymocyte apoptosis. SR-BI+/+ HDL significantly enhanced GC-induced thymocyte apoptosis but SR-BI−/− HDL had no such activity. Further study revealed that SR-BI+/+ HDL modulates GC-induced thymocyte apoptosis via promoting glucocorticoid receptor translocation, but SR-BI−/− HDL loses such regulatory activity. To understand why SR-BI−/− HDL loses its regulatory activity, we analyzed HDL cholesterol contents. There was 3-fold enrichment of unesterified cholesterol in SR-BI−/− HDL compared with SR-BI+/+ HDL. Normalization of unesterified cholesterol in SR-BI−/− HDL by probucol administration or LCAT expression restored GC-induced thymocyte apoptosis, and incorporating unesterified cholesterol into SR-BI+/+ HDL rendered SR-BI+/+ HDL dysfunctional. Using lckCre-GRfl/fl mice in whom thymocytes lack CLP-induced thymocyte apoptosis, we showed that lckCre-GRfl/fl mice were significantly more susceptible to CLP-induced septic death than GRfl/fl control mice, suggesting that GC-induced thymocyte apoptosis is required for protection against sepsis. Conclusions The findings in this study reveal a novel regulatory mechanism of thymocyte apoptosis in sepsis by SR-BI and HDL. PMID:24603680

  7. NASCENTES ANTROPOGÊNICAS: PROCESSOS TECNOGÊNICOS E HIDROGEOMORFOLÓGICOS

    Directory of Open Access Journals (Sweden)

    Miguel Fernandes Felippe

    2014-04-01

    Full Text Available Nascentes de cursos d’água são sistemas ambientais em que a água emerge naturalmente do meio subterrâneo integrando a rede de drenagem superficial. Porém, no Tecnógeno, as intervenções humanas podem criar condições necessárias para a exfiltração da água onde originalmente isso não ocorreria. Se essa nova zona de descarga se conecta com a rede de drenagem via fluxos superficiais, ela pode ser considerada uma nascente de acordo com os conceitos acadêmicos mais aceitos. Entretanto, por sua origem ter sido induzida pelos seres humanos, esta deve ser considerada uma nascente antropogênica. Esse trabalho aborda conceitualmente as nascentes antropogênicas baseado em trabalhos de campo realizados no espaço metropolitano de Belo Horizonte-MG, explorando suas características principais. Além disso, são evidenciadas as diferenças entre a influência humana sobre as nascentes e a antropogenia desses sistemas, identificando os processos antrópicos que podem originar nascentes e discutindo as possíveis conseqüências dessas intervenções. Por fim, seis casos ilustrativos são apresentados, demonstrando como as nascentes antropogênicas podem ser formadas e suas conseqüências para a dinâmica hidrogeomorfológica.

  8. Impaired HDL2-mediated cholesterol efflux is associated with metabolic syndrome in families with early onset coronary heart disease and low HDL-cholesterol level

    Science.gov (United States)

    Paavola, Timo; Kuusisto, Sanna; Jauhiainen, Matti; Kakko, Sakari; Kangas-Kontio, Tiia; Metso, Jari; Soininen, Pasi; Ala-Korpela, Mika; Bloigu, Risto; Hannuksela, Minna L.; Savolainen, Markku J.

    2017-01-01

    Objective The potential of high-density lipoproteins (HDL) to facilitate cholesterol removal from arterial foam cells is a key function of HDL. We studied whether cholesterol efflux to serum and HDL subfractions is impaired in subjects with early coronary heart disease (CHD) or metabolic syndrome (MetS) in families where a low HDL-cholesterol level (HDL-C) predisposes to early CHD. Methods HDL subfractions were isolated from plasma by sequential ultracentrifugation. THP-1 macrophages loaded with acetyl-LDL were used in the assay of cholesterol efflux to total HDL, HDL2, HDL3 or serum. Results While cholesterol efflux to serum, total HDL and HDL3 was unchanged, the efflux to HDL2 was 14% lower in subjects with MetS than in subjects without MetS (pHDL2 was associated with components of MetS such as plasma HDL-C (r = 0.76 in men and r = 0.56 in women, pHDL2 was reduced in men with early CHD (pHDL-C. The phospholipid content of HDL2 particles was a major correlate with the efflux to HDL2 (r = 0.70, pHDL2 to total HDL was associated with MetS (pHDL2 is a functional feature of the low HDL-C state and MetS in families where these risk factors predispose to early CHD. The efflux to HDL2 related to the phospholipid content of HDL2 particles but the phospholipid content did not account for the impaired efflux in cardiometabolic disease, where a combination of low level and poor quality of HDL2 was observed. PMID:28207870

  9. ATP Synthase β-Chain Overexpression in SR-BI Knockout Mice Increases HDL Uptake and Reduces Plasma HDL Level

    Directory of Open Access Journals (Sweden)

    Kexiu Song

    2014-01-01

    Full Text Available HDL cholesterol is known to be inversely correlated with cardiovascular disease due to its diverse antiatherogenic functions. SR-BI mediates the selective uptake of HDL-C. SR-BI knockout diminishes but does not completely block the transport of HDL; other receptors may be involved. Ectopic ATP synthase β-chain in hepatocytes has been previously characterized as an apoA-I receptor, triggering HDL internalization. This study was undertaken to identify the overexpression of ectopic ATP synthase β-chain on DIL-HDL uptake in primary hepatocytes in vitro and on plasma HDL levels in SR-BI knockout mice. Human ATP synthase β-chain cDNA was delivered to the mouse liver by adenovirus and GFP adenovirus as control. The adenovirus-mediated overexpression of β-chain was identified at both mRNA and protein levels on mice liver and validated by its increasing of DiL-HDL uptake in primary hepatocytes. In response to hepatic overexpression of β-chain, plasma HDL-C levels and cholesterol were reduced in SR-BI knockout mice, compared with the control. The present data suggest that ATP synthase β-chain can serve as the endocytic receptor of HDL, and its overexpression can reduce plasma HDL-C.

  10. Postmenopausal Women Have Higher HDL and Decreased Incidence of Low HDL than Premenopausal Women with Metabolic Syndrome.

    Science.gov (United States)

    Fernandez, Maria Luz; Murillo, Ana Gabriela

    2016-03-16

    It is well known that plasma lipids, waist circumference (WC) and blood pressure (BP) increase following menopause. In addition, there is a perceived notion that plasma high-density lipoprotein-cholesterol (HDL-C) concentrations also decrease in postmenopausal women. In this cross-sectional study, we evaluated plasma lipids, fasting glucose, anthropometrics and BP in 88 post and 100 pre-menopausal women diagnosed with metabolic syndrome. No differences were observed in plasma low-density lipoprotein-cholesterol cholesterol, triglycerides, fasting glucose or systolic and diastolic BP between groups. However, plasma HDL-C was higher (p HDL (HDL-C (r = -0.148, p HDL-C (r = -0.258, p HDL-C. Interestingly, there was a positive correlation between age and plasma HDL-C (r = 0.237 p HDL is decreased by visceral fat and overall weight, low HDL is not a main characteristic of metabolic syndrome in postmenopausal women. Further, HDL appears to increase, not decrease, with age.

  11. Lower levels of total HDL and HDL3 cholesterol are associated with albuminuria in normoalbuminuric Type 1 diabetic patients.

    Science.gov (United States)

    Bulum, T; Kolaric, B; Duvnjak, L

    2013-09-01

    Previous studies have suggested a positive association between dyslipidemia and chronic kidney disease, but sparse data are available on the relation of lipids and urinary albumin excretion rate (UAE) in normoalbuminuric patients with normal renal function. The aim of this study was to evaluate the associations of serum lipids, including total, LDL, HDL, HDL2, HDL3 cholesterol, and triglyceride levels with UAE in normoalbuminuric Type 1 diabetic (T1D) patients. Study included 313 normoalbuminuric T1D patients with normal renal function and before any interventions with statins, ACE inhibitors or angiotensin II receptor blockers. Subjects were classified as low-normoalbuminuric (UAEHDL (p=0.02) and HDL3 cholesterol (p=0.01) levels were higher in low-normoalbuminuric subjects compared to high-normoalbuminuric subjects. In logistic regression analysis, after adjustment for age, sex, BMI, duration of diabetes and HbA1c, lower total HDL and HDL3 cholesterol levels were significantly associated with risk of higher UAE in our normoalbuminuric subjects (p≤0.01), with odds ratios of 0.34 to 0.43. Elevated total HDL and HDL3 cholesterol levels are associated with lower UAE in normoalbuminuric T1D patients. However, whether the detection of elevated total HDL and HDL3 cholesterol levels in T1D patients has protective value for development of microalbuminuria needs to be assessed in further follow-up studies.

  12. Nascent multicellular life and the emergence of individuality

    Indian Academy of Sciences (India)

    Silvia De Monte; Paul B Rainey

    2014-04-01

    The evolution of multicellular organisms from unicellular ancestors involves a shift in the level at which selection operates. It is usual to think about this shift in terms of the emergence of traits that cause heritable differences in reproductive output at the level of nascent collectives. Defining these traits and the causes of their origin lies at the heart of understanding the evolution of multicellular life. In working toward a mechanistic, take-nothing-for-granted account, we begin by recognizing that the standard Lewontin formulation of properties necessary and sufficient for evolution by natural selection does not necessarily encompass Darwinian evolution in primitive collectives where parent-offspring relationships may have been poorly defined. This, we suggest, limits the ability to conceptualize and capture the earliest manifestations of Darwinian properties. By way of solution we propose a relaxed interpretation of Lewontin’s conditions and present these in the form of a set of necessary requirements for evolution by natural selection based upon the establishment of genealogical connections between recurrences of collectives. With emphasis on genealogy – as opposed to reproduction – it is possible to conceive selection acting on collectives prior to any manifestation of heritable variance in fitness. Such possibility draws attention to the evolutionary emergence of traits that strengthen causal relationships between recurrences – traits likely to underpin the emergence of forms of multiplication that establish parent-offspring relationships. Application of this framework to collectives of marginal status, particularly those whose recurrence is not defined by genealogy, makes clear that change at the level of collectives need not arise from selection acting at the higher level. We conclude by outlining applicability of our framework to loosely defined collectives of cells, such as those comprising the slugs of social amoeba and microbes that

  13. ApoE-containing HDL and the development of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Zbigniew Zdrojewski

    2015-06-01

    Full Text Available The current state of knowledge about the role of high density lipoproteins (HDL indicates that their anti-atherogenic function is mainly related to the effectiveness of their actions (mostly to the participation in reverse cholesterol transport from tissues to liver rather than the concentration of HDL itself. HDLs are highly heterogeneous in their structure, lipid and protein composition and metabolic pathways and individual HDL subpopulations differ in their biological activity and effectiveness of anti-atherogenic actions. Apolipoproteins play a key role in HDL metabolism, therefore their presence in lipoproteins is one of the main criterion for HDL classification. According to this criterion HDLs containing apolipoprotein E, called HDL-apoE, are distinguished. Although the anti-atherogenic role of apo E has been demonstrated in many scientific reports, understanding of the mechanisms of formation, transformation and the role of HDL-apoE is still the aim of intense research. The results of epidemiological studies are inconclusive; some of them have demonstrated that high HDL- -apoE concentration has been associated with lower risk of developing coronary heart disease (CHD, while other studies have shown that high levels of HDL-apoE has been an independent risk factor for cardiovascular events and positively correlated with other risk factors for CHD.

  14. ApoE-containing HDL and the development of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Agnieszka Ćwiklińska

    2015-01-01

    Full Text Available The current state of knowledge about the role of high density lipoproteins (HDL indicates that their anti-atherogenic function is mainly related to the effectiveness of their actions (mostly to the participation in reverse cholesterol transport from tissues to liver rather than the concentration of HDL itself. HDLs are highly heterogeneous in their structure, lipid and protein composition and metabolic pathways and individual HDL subpopulations differ in their biological activity and effectiveness of anti-atherogenic actions. Apolipoproteins play a key role in HDL metabolism, therefore their presence in lipoproteins is one of the main criterion for HDL classification. According to this criterion HDLs containing apolipoprotein E, called HDL-apoE, are distinguished. Although the anti-atherogenic role of apo E has been demonstrated in many scientific reports, understanding of the mechanisms of formation, transformation and the role of HDL-apoE is still the aim of intense research. The results of epidemiological studies are inconclusive; some of them have demonstrated that high HDL- -apoE concentration has been associated with lower risk of developing coronary heart disease (CHD, while other studies have shown that high levels of HDL-apoE has been an independent risk factor for cardiovascular events and positively correlated with other risk factors for CHD.

  15. Genetic causes of high and low serum HDL-cholesterol

    Science.gov (United States)

    Weissglas-Volkov, Daphna; Pajukanta, Päivi

    2010-01-01

    Plasma levels of HDL cholesterol (HDL-C) have a strong inherited basis with heritability estimates of 40-60%. The well-established inverse relationship between plasma HDL-C levels and the risk of coronary artery disease (CAD) has led to an extensive search for genetic factors influencing HDL-C concentrations. Over the past 30 years, candidate gene, genome-wide linkage, and most recently genome-wide association (GWA) studies have identified several genetic variations for plasma HDL-C levels. However, the functional role of several of these variants remains unknown, and they do not always correlate with CAD. In this review, we will first summarize what is known about HDL metabolism, monogenic disorders associated with both low and high HDL-C levels, and candidate gene studies. Then we will focus this review on recent genetic findings from the GWA studies and future strategies to elucidate the remaining substantial proportion of HDL-C heritability. Comprehensive investigation of the genetic factors conferring to low and high HDL-C levels using integrative approaches is important to unravel novel pathways and their relations to CAD, so that more effective means of diagnosis, treatment, and prevention will be identified. PMID:20421590

  16. Increasing HDL-C levels with medication: current perspectives.

    Science.gov (United States)

    Smit, Roelof Aj; Jukema, J Wouter; Trompet, Stella

    2017-08-01

    To date, observational studies have repeatedly demonstrated an inverse association between HDL cholesterol (HDL-C) levels and cardiovascular outcomes. Although the efficacy of established HDL-modifying treatment strategies have been examined in multiple large-scale phase III trials, findings from these experimental studies conflict with the hypothesis that HDL-C levels are atheroprotective. In this review, we describe the trial evidence to date, and attempt to place these results in the broader context of recent hypotheses for the association between HDL-C levels and clinical outcomes. Both translational and genetic studies are in line with the hypothesis that HDL-C levels do not hold causal importance for cardiovascular risk reduction. In addition to its possible role as a biomarker for other atherogenic lipoproteins, efforts should be made to elucidate HDLs' role in lipoprotein flux, which is increasingly being linked to surrogate outcomes of importance to cardiovascular epidemiology. In the future, it will be of great importance to link this measure of HDL functionality to clinical endpoints. Although trial evidence does not support an atheroprotective role of overall HDL-C plasma levels, HDL function/lipoprotein flux holds great promise for the development of novel therapeutic approaches.

  17. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

    Science.gov (United States)

    Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2012-04-15

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together

  18. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes

    Science.gov (United States)

    Storey, Stephen M.; McIntosh, Avery L.; Huang, Huan; Landrock, Kerstin K.; Martin, Gregory G.; Landrock, Danilo; Payne, H. Ross; Atshaves, Barbara P.; Kier, Ann B.

    2012-01-01

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null mice and hepatocytes. Taken together

  19. GALNT2 effect on HDL-cholesterol and triglycerides levels in humans: Evidence of pleiotropy?

    Science.gov (United States)

    Di Paola, R; Marucci, A; Trischitta, V

    2017-04-01

    A wide range of studies both in humans and animal models point GALNT2 as a shaper of serum HDL-C and TG levels. Available data in humans indicate that, while under conditions of extreme GALNT2 loss-of-function HDL-C is the main target, a fine-tuning of GALNT2 changes is mostly associated with TG levels. Understanding whether different degrees of GALNT2 change do modulate different serum lipid fractions and, if so, addressing the mechanisms underlying such pleiotropic effects has the potential not only to improve our understanding of HDL-C and TG metabolism, but also to make GALNT2 becoming a target for treating atherogenic dyslipidemia and related clinical events. Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

  20. An Institutional Perspective on Business Planning Activities for Nascent Entrepreneurs in Sweden and the US

    Directory of Open Access Journals (Sweden)

    Benson Honig

    2013-11-01

    Full Text Available We compared nascent characteristics and behaviors leading to business planning activities in Sweden with the United States (US, examining the effects of institutional pressures exerted in the different countries. We analyzed institutional factors leading 362 Swedish and 347 US entrepreneurs to write plans during a two-year period. We show that national cultures moderate how institutional pressures influence nascent behaviors, questioning generic applications of institutional theory. We found business planning behaviors moderated by nationality, showing significant and negative effects for business classes in the US. Implications are drawn for institutional theory and the study of nascent businesses, as well as for normative business planning literature and practice of nascent businesses.

  1. Live cell imaging of the nascent inactive X chromosome during the early differentiation process of naive ES cells towards epiblast stem cells.

    Directory of Open Access Journals (Sweden)

    Aurélia Guyochin

    Full Text Available Random X-chromosome inactivation ensures dosage compensation in mammals through the transcriptional silencing of one of the two X chromosomes present in each female cell. Silencing is initiated in the differentiating epiblast of the mouse female embryos through coating of the nascent inactive X chromosome by the non-coding RNA Xist, which subsequently recruits the Polycomb Complex PRC2 leading to histone H3-K27 methylation. Here we examined in mouse ES cells the early steps of the transition from naive ES cells towards epiblast stem cells as a model for inducing X chromosome inactivation in vitro. We show that these conditions efficiently induce random XCI. Importantly, in a transient phase of this differentiation pathway, both X chromosomes are coated with Xist RNA in up to 15% of the XX cells. In an attempt to determine the dynamics of this process, we designed a strategy aimed at visualizing the nascent inactive X-chromosome in live cells. We generated transgenic female XX ES cells expressing the PRC2 component Ezh2 fused to the fluorescent protein Venus. The fluorescent fusion protein was expressed at sub-physiological levels and located in nuclei of ES cells. Upon differentiation of ES cell towards epiblast stem cell fate, Venus-fluorescent territories appearing in interphase nuclei were identified as nascent inactive X chromosomes by their association with Xist RNA. Imaging of Ezh2-Venus for up to 24 hours during the differentiation process showed survival of some cells with two fluorescent domains and a surprising dynamics of the fluorescent territories across cell division and in the course of the differentiation process. Our data reveal a strategy for visualizing the nascent inactive X chromosome and suggests the possibility for a large plasticity of the nascent inactive X chromosome.

  2. Endothelial lipase is a major determinant of HDL level

    Energy Technology Data Exchange (ETDEWEB)

    Ishida, Tatsuro; Choi, Sungshin; Kundu, Ramendra K.; Hirata, Ken-Ichi; Rubin, Edward M.; Cooper, Allen D.; Quertermous, Thomas

    2003-01-30

    For the past three decades, epidemiologic studies have consistently demonstrated an inverse relationship between plasma HDL cholesterol (HDL-C) concentrations and coronary heart disease (CHD). Population-based studies have provided compelling evidence that low HDL-C levels are a risk factor for CHD, and several clinical interventions that increased plasma levels of HDL-C were associated with a reduction in CHD risk. These findings have stimulated extensive investigation into the determinants of plasma HDL-C levels. Turnover studies using radiolabeled apolipoprotein A-I, the major protein component of HDL, suggest that plasma HDL-C concentrations are highly correlated with the rate of clearance of apolipoprotein AI. However, the metabolic mechanisms by which HDL are catabolized have not been fully defined. Previous studies in humans with genetic deficiency of cholesteryl ester transfer protein, and in mice lacking the scavenger receptor BI (SR-BI), have demonstrated that these proteins participate in the removal of cholesterol from HDL, while observations in individuals with mutations in hepatic lipase indicate that this enzyme hydrolyzes HDL triglycerides. In this issue of the JCI, reports from laboratories of Tom Quertermous and Dan Rader now indicate that endothelial lipase (LIPG), a newly identified member of the lipase family, catalyzes the hydrolysis of HDL phospholipids and facilitates the clearance of HDL from the circulation. Endothelial lipase was initially cloned by both of these laboratories using entirely different strategies. Quertermous and his colleagues identified endothelial lipase as a transcript that was upregulated in cultured human umbilical vein endothelial cells undergoing tube formation, whereas the Rader group cloned endothelial lipase as a transcript that was upregulated in the human macrophage-like cell line THP-1 exposed to oxidized LDL. Database searches revealed that endothelial lipase shows strong sequence similarity to lipoprotein

  3. Pre-β1 HDL in type 2 diabetes mellitus.

    Science.gov (United States)

    Shiu, S W; Wong, Y; Tan, K C

    2017-08-01

    Pre-β1 HDL, being a major acceptor of free cholesterol from cells, plays an important role in reverse cholesterol transport. This study was performed to determine whether abnormalities in pre-β1 HDL concentration were present in type 2 diabetes irrespective of their HDL-cholesterol levels, and the impact on cholesterol efflux. 640 type 2 diabetic patients with or without cardiovascular disease (CVD) and 360 non-diabetic controls matched for serum HDL-cholesterol levels were recruited. Plasma pre-β1 HDL was measured by ELISA, and cholesterol efflux to serum, mediated by ATP-binding cassette transporter A1 (ABCA1), was determined by measuring the transfer of [3H]cholesterol from cultured cells expressing ABCA1 to the medium containing the tested serum. Despite the diabetic subjects having matched HDL-cholesterol and total apoA1 as controls, plasma pre-β1 HDL was significantly reduced in both male (p diabetic patients (p HDL level. Serum capacity to induce ABCA1-mediated cholesterol efflux was impaired in the diabetic group (p HDL (Pearson's r = 0.38, p diabetes status, smoking, apoA1, triglyceride and LDL. Plasma pre-β1 HDL level was significantly decreased in type 2 diabetes and was associated with a reduction in cholesterol efflux mediated by ABCA1. Our data would suggest that low pre-β1 HDL might cause impairment in reverse cholesterol transport in type 2 diabetes. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. DESENVOLVIMENTO DE UMA TIPOLOGIA HIDROGEOMORFOLÓGICA DE NASCENTES BASEADA EM ESTATÍSTICA NEBULOSA MULTIVARIADA

    Directory of Open Access Journals (Sweden)

    Miguel Fernandes Felippe

    2014-09-01

    Full Text Available As nascentes de cursos d’água são sistemas hidrogeomorfológicos complexos, caracterizados por uma grande variabilidade de seus elementos estruturantes. Esta heterogeneidade ainda pouco conhecida cria dificuldades para os processos de gestão ambiental, pois, em teoria, cada nascente responde a perturbações de maneira diferente. Nesse sentido, este trabalho tem como objetivo desenvolver uma tipologia de nascentes com base em suas características hidrogeomorfológicas que sistematize sua heterogeneidade, sem perder seus aspectos individuais. Para atingir esta meta um método de máxima verossimilhança baseado na teoria dos conjuntos nebulosos foi usado para criar perfis multivariados para 79 nascentes catalogadas em três parques urbanos de Belo Horizonte - MG. Após uma série de testes estatísticos, propuseram-se seis tipos básicos no qual as nascentes podem ser enquadradas. No entanto, o principal avanço desta técnica é permitir a comparação entre os diferentes graus de pertencimento de cada nascente em cada tipo criado, auxiliando na compreensão da sua diversidade, sem esconder a sua heterogeneidade.

  5. 缺血性脑卒中患者TC/HDL-C、TG/HDL-C比值与HDL亚类分布的关系%Relationship between HDL subclasses and TC/HDL-C, TG/HDL-C ratio in Ischemic Stroke

    Institute of Scientific and Technical Information of China (English)

    韩瑛; 陈志军; 卢新华; 邓华菲; 王岐本; 孙陶利; 龙石银; 田英

    2014-01-01

    Objective To investigate the relationship between HDL subclasses and TC/HDL-C ,TG/HDL-C ratio in ischemic stroke patients .Methods According to the ratio of TC/HDL-C and TG/HDL-C ,61 ischemic stroke patients were divided into three groups ,respectively .HDL subclasses were quantitated by two-dimension-al gel electrophoresis .Results Accompanied with the increase of TC/HDL-C and TG/HDL-C ratio in ischemic stroke patients ,the levels of small-sized preβ1 -HDL showed a trend of rise ,and the contents of large-sized of HDL2a and HDL2b showed a trend of decrease .Analysis of correlation found that TG ,TC/HDL-C and TG/HDL-C showed a positive correlation with small-sized preβ1 -HDL ( P <0 .05 ) ,but a negative correlation with large-sized HDL2a and HDL2b ( P <0 .05) ,HDL-C showed a positive correlation with all particles of HDL in isch-emic stroke patients ( P <0 .05 ) . Conclusion The increase of TC/HDL -C and TG/HDL -C were associated with the mature of HDL metabolism and the weakened of reverse cholesterol transport .%目的:探讨缺血性脑卒中患者总胆固醇/高密度脂蛋白醇(TC/HDL-C)、甘油三酯/高密度脂蛋白醇(TG/HDL-C )比值与与血浆中高密度脂蛋白(HDL )亚类含量的关系。方法根据TC/HDL-C和TG/HDL-C比值分别将61例缺血性脑卒中患者分为高、中、低比值组,采用双向电泳-免疫印迹检测法分析HDL亚类的组成、含量及分布特征。结果在缺血性脑卒中患者中,随着TC/HDL-C或TG/HDL-C比值增大,小颗粒的preβ1-HDL含量呈升高趋势,大颗粒的HDL2 a 、HDL2 b含量呈降低趋势。相关性分析发现,缺血性脑卒中患者血浆TG、TC/HDL-C和TG/HDL-C与小颗粒preβ1-HDL含量呈正相关( P <0.05),而与大颗粒HDL2a及HDL2b含量呈负相关( P <0.05);HDL-C和apoA1与HDL各亚类呈正相关( P<0.05)。结论缺血性脑卒中患者中TC/HDL-C或TG/HDL-C比值的升高与HDL成熟代谢受阻、胆固醇逆转运作用减弱有关。

  6. Inflammation modulates human HDL composition and function in vivo

    Science.gov (United States)

    Inflammation may directly impair HDL functions, in particular reverse cholesterol transport (RCT), but limited data support this concept in humans. Our study was designed to investigate this relationship. We employed low-dose human endotoxemia to assess the effects of inflammation on HDL and RCT-rel...

  7. Printed Circuit Board Design (PCB) with HDL Designer

    Science.gov (United States)

    Winkert, Thomas K.; LaFourcade, Teresa

    2004-01-01

    Contents include the following: PCB design with HDL designer, design process and schematic capture - symbols and diagrams: 1. Motivation: time savings, money savings, simplicity. 2. Approach: use single tool PCB for FPGA design, more FPGA designs than PCB designers. 3. Use HDL designer for schematic capture.

  8. Low HDL cholesterol is associated with lower gray matter volume in cognitively healthy adults

    Directory of Open Access Journals (Sweden)

    Michael A Ward

    2010-07-01

    Full Text Available Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE genotype or family history of Alzheimer’s disease (FHAD alters this effect. Methods: T1-weighted MRI was used to examine regional brain gray matter (GM and white matter (WM in 183 individuals (58.4 ± 8.0 years using voxel-based morphometry. A nonparametric multiple linear regression model was used to assess the effect of high-density lipoprotein (HDL and non-HDL cholesterol, APOE, and FHAD on regional GM and WM volume. A post hoc analysis was used to assess whether any significant correlations found within the volumetric analysis had an effect on cognition. Results: HDL was positively correlated with GM volume in the bilateral temporal poles, middle temporal gyri, temporo-occipital gyri, and left superior temporal gyrus and parahippocampal region. This effect was independent of APOE and FHAD. A significant association between HDL and the Brief Visuospatial Memory Test was found. Additionally, GM volume within the right middle temporal gyrus, the region most affected by HDL, was significantly associated with the Controlled Oral Word Association Test and the Center of Epidemiological Studies Depression Scale. Conclusions: These findings suggest that adults with decreased levels of HDL cholesterol may be experiencing cognitive changes and GM reductions in regions associated with neurodegenerative disease and therefore, may be at greater risk for future cognitive decline.

  9. HDL as a drug and nucleic acid delivery vehicle

    Directory of Open Access Journals (Sweden)

    Andras G Lacko

    2015-10-01

    Full Text Available This review is intended to evaluate the research findings and potential clinical applications of drug transport systems, developed based on the concepts of the structure/function and physiological role(s of high density lipoprotein=type nanoparticles. These macromolecules provide targeted transport of cholesteryl esters (a highly lipophilic payload in their natural/physiological environment. The property of accommodating highly water insoluble constituents in their core region enables HDL type nanoparticles to effectively transport hydrophobic drugs upon intravenous administration. Even though the application of reconstituted HDL in the treatment of a number of diseases is reviewed, the primary focus is on the application of HDL type drug delivery agents in cancer chemotherapy. The use of both native and synthetic HDL as drug delivery agents are compared to evaluate their respective potentials for commercial and clinical development. The current status and future perspectives for HDL type nanoparticles are discussed, including current obstacles and future applications in therapeutics.

  10. Genetic association analysis of polymorphisms in PSD3 gene with obesity, type 2 diabetes, and HDL cholesterol.

    Science.gov (United States)

    Gong, Shaoqing; Xu, Chun; Wang, Liang; Liu, Ying; Owusu, Daniel; Bailey, Beth A; Li, Yujing; Wang, Kesheng

    2017-04-01

    The pleckstrin and Sec7 domain-containing 3 (PSD3) gene has been linked to immune diseases. We examined whether the genetic variants within the PSD3 gene are associated with obesity, type 2 diabetes (T2D), and high-density lipoprotein (HDL) cholesterol level. Multiple logistic regression model and linear regression model were used to examine the associations of 259 single nucleotide polymorphisms (SNPs) within the PSD3 gene with obesity and T2D as binary traits, and HDL level as a continuous trait using the Marshfield data, respectively. A replication study of obesity was conducted using the Health Aging and Body Composition (Health ABC) sample. 23SNPs were associated with obesity (pHDL level (top SNP rs13254772 with p=2.79×10(-3)) in the Marshfield data; meanwhile rs7009615 was associated with both T2D (p=0.038) and HDL level (p=4.44×10(-3)). In addition, haplotype analyses further supported the results of single SNP analysis. Common variants in PSD3 were associated with obesity, T2D and HDL level. These findings add important new insights into the pathogenesis of obesity, T2D and HDL cholesterol. Published by Elsevier B.V.

  11. Coronary Disease Person Blood Serum TG/HDL-C、LDL-C/HDL-C Relevant Research%冠心病人血清TG/HDL-C、LDL-C/HDL-C的相关性研究

    Institute of Scientific and Technical Information of China (English)

    王健

    2009-01-01

    目的:测定血清低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和总胆固醇(TC)、甘油三酯(TG)等血脂指标,探讨TG/HDL-C、LDL-C/HDL-C比值水平;在冠心病人和正常人群中的分布及与冠心病的相关性.方法:应用O-LYMPUS2700型全自动生化分析仪测定汉族199例冠心病患者和189例正常人群静脉血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)水平,并计算出TG/HDL-C、LDL-C/HDL-C比值.结果:冠心病人血清TG/HDL-C、LDL-C/HDL-C比值分别为2.24±0.41 mmol/L,1.48±0.49mmol/L.比正常对照组显著增高(P<0.01),其中LDL-C/HDL-C比值较TG/HDL-C比值差异更显著.结论:冠心病人血清TG、LDL-C显著增加,HDL-C水平显著下降.联合应用TG/HDL-C、LDL-C/HDL-C比值作为CHD的预测指标,较客观地反映出冠心病人的非均一性改变,能及时发现CHD高危病人,进行早期合理干预,对防止AS和CHD的发生发展有一定的临床意义.

  12. Changes in triglyceride, HDL-C, and non-HDL-C levels in patients with acute coronary syndrome.

    Science.gov (United States)

    Koncsos, Péter; Fülöp, Péter; Juhász, Imre; Bíró, Klára; Márk, László; Simonyi, Gábor; Paragh, György

    2016-12-01

    Changes in high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) levels have been linked to residual cardiovascular risk, whereas non-HDL-C levels have been shown to be more predictive of cardiovascular risk than are low-density lipoprotein cholesterol (LDL-C) levels. We aimed to investigate the impact of HDL-C, TG, and non-HDL-C levels on acute coronary syndrome (ACS) risk with on-target LDL-C levels. In all, 424 Caucasian patients aged over 50 years who had LDL-C levels below 3.4 mmol/l with a first or subsequent ACS event were enrolled in a multicenter, retrospective study. Lipid samples were collected within 4 days after the cardiovascular event. The subjects of the age-matched, gender-balanced control group (n = 443) had LDL-C levels below 3.4 mmol/l and were free of cardiovascular diseases. Patients with ACS had significantly higher TG and lower HDL-C levels compared with the control patients; however, we did not find any significant difference regarding non-HDL-C levels between the two groups. In regression analysis, the risk of coronary heart disease increased significantly with 1 standard deviation (SD) increase in TG and 1 SD decrease in HDL-C levels. High TG and low HDL-C levels may contribute to residual cardiovascular risk in patients with well-controlled LDL-C levels; however, non-HDL-C levels at admission did not seem to be predictive for patients with ACS. Detection and treatment of secondary lipid targets such as high TG and low HDL-C levels may be important for the prevention of cardiovascular diseases.

  13. Is non-HDL-cholesterol a better predictor of long-term outcome in patients after acute myocardial infarction compared to LDL-cholesterol? : a retrospective study.

    Science.gov (United States)

    Wongcharoen, Wanwarang; Sutthiwutthichai, Satjatham; Gunaparn, Siriluck; Phrommintikul, Arintaya

    2017-01-05

    It has recently been shown that non-high density lipoprotein cholesterol (non-HDL-C) may be a better predictor of cardiovascular risk than low density lipoprotein cholesterol (LDL-C). Based on known ethic differences in lipid parameters and cardiovascular risk prediction, we sought to study the predictability of attaining non-HDL-C target and long-term major adverse cardiovascular event (MACE) in Thai patients after acute myocardial infarction (AMI) compared to attaining LDL-C target. We retrospectively obtained the data of all patients who were admitted at Maharaj Nakorn Chiang Mai hospital due to AMI during 2006-2013. The mean non-HDL-C and LDL-C during long-term follow-up were used to predict MACE at each time point. The patients were classified as target attainment if non-HDL-C HDL-C target, 23.7% achieved LDL-C target and 21.2% experienced MACEs. LDL-C and non-HDL-C were directly compared in Cox regression model. Compared with non-HDL-C HDL-C of >130 mg/dl had higher incidence of MACEs (HR 3.15, 95% CI 1.46-6.80, P = 0.003). Surprisingly, LDL-C >100 mg/dl was associated with reduced risk of MACE as compared to LDL HDL-C level. Non-attaining non-HDL-C goal predicted MACE at long-term follow-up after AMI whereas non-attaining LDL-C goal was not associated with the higher risk. Therefore, non-HDL-C may be a more suitable target of dyslipidemia treatment than LDL-C in patients after AMI.

  14. Two-year follow-up of patients with septic shock presenting with low HDL: the effect upon acute kidney injury, death and estimated glomerular filtration rate.

    Science.gov (United States)

    Roveran Genga, K; Lo, C; Cirstea, M; Zhou, G; Walley, K R; Russell, J A; Levin, A; Boyd, J H

    2017-05-01

    Sepsis is associated with decreased levels of high-density lipoprotein (HDL) cholesterol. HDL has anti-inflammatory properties, and the use of Apo A-I mimetic peptides is associated with renal function improvement in animal models of sepsis. However, it is not known whether decreased HDL level results in impaired renal function in human sepsis. We investigated whether low levels of HDL conferred an increased risk of sepsis-associated acute kidney injury (AKI) or long-term decreased estimated glomerular filtration rate (eGFR) after sepsis. HDL concentration (mg dL(-1) ) was measured in plasma samples from 180 patients with septic shock at admission to the Emergency Department (ED). We divided the patients using median HDL as a cut-off value and assessed the frequency of sepsis-associated AKI and long-term decreased eGFR after sepsis. Univariate and multivariate analyses were performed. Patients with low HDL had a significantly greater frequency of KDIGO 2 or 3 sepsis-associated AKI [39/90 (43.3%) vs. 12/90 (13.3%), P HDL. The adjusted OR for sepsis-associated AKI and decreased eGFR after sepsis in the lower HDL group was 2.80 (95% CI 1.08-7.25, P = 0.033) and 5.45 (95% CI 1.57-18.93, P = 0.008), respectively. Low HDL levels during sepsis are associated with increased risk of sepsis-associated AKI, and/or subsequent decreased eGFR. These results suggest that HDL may be involved and/or may be a marker of kidney injury during and after sepsis. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  15. Molecular Dynamics Simulation and Experimental Studies of Gold Nanoparticle Templated HDL-like Nanoparticles for Cholesterol Metabolism Therapeutics.

    Science.gov (United States)

    Lai, Cheng-Tsung; Sun, Wangqiang; Palekar, Rohun U; Thaxton, C Shad; Schatz, George C

    2017-01-18

    High-density lipoprotein (HDL) plays an important role in the transport and metabolism of cholesterol. Mimics of HDL are being explored as potentially powerful therapeutic agents for removing excess cholesterol from arterial plaques. Gold nanoparticles (AuNPs) functionalized with apolipoprotein A-I and with the lipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-[3-(2-pyridyldithio)propionate] have been demonstrated to be robust acceptors of cellular cholesterol. However, detailed structural information about this functionalized HDL AuNP is still lacking. In this study, we have used X-ray photoelectron spectroscopy and lecithin/cholesterol acyltransferase activation experiments together with coarse-grained and all-atom molecular dynamics simulations to model the structure and cholesterol uptake properties of the HDL AuNP construct. By simulating different apolipoprotein-loaded AuNPs, we find that lipids are oriented differently in regions with and without apoA-I. We also show that in this functionalized HDL AuNP, the distribution of cholesteryl ester maintains a reverse concentration gradient that is similar to the gradient found in native HDL.

  16. Whey protein improves HDL/non-HDL ratio and body weight gain in rats subjected to the resistance exercise

    Directory of Open Access Journals (Sweden)

    Kely Raspante Teixeira

    2012-12-01

    Full Text Available The aim of this study was to evaluate the effects of resistance exercise, such as weight-lifting (WL on the biochemical parameters of lipid metabolism and cardiovascular disease risk in the rats fed casein (control or whey protein (WP diets. Thirty-two male Fisher rats were randomly assigned to sedentary or exercise-trained groups and were fed control or WP diets. The WL program consisted of inducing the animals to perform the sets of jumps with weights attached to the chest. After seven weeks, arteriovenous blood samples were collected for analysis. The WL or WP ingestion were able to improve the lipid profile, reducing the TC and non-HDL cholesterol concentrations, but only WP treatment significantly increased the serum HDL concentrations, thereby also affecting the TC/HDL and HDL/non-HDL ratios. However, WL plus WP was more effective in improving the HDL/non-HDL ratio than the exercise or WP ingestion alone and the body weight gain than exercise without WP ingestion.

  17. The alpha-chain of the nascent polypeptide-associated complex binds to and regulates FADD function.

    Science.gov (United States)

    Stilo, Romania; Liguoro, Domenico; di Jeso, Bruno; Leonardi, Antonio; Vito, Pasquale

    2003-04-18

    FADD protein is a critical mediator of signal transduction pathways activated by several members of the TNF-receptor gene superfamily. Recently, an induced proximity model has been proposed to interpret FADD-mediated signaling events. According to this model, FADD facilitates signaling by inducing clusters of effector molecules in proximity of the activated receptor complex. An important corollary of the induced-proximity model is that FADD protein should not form oligomers in the absence of receptor stimulation. Here we show that, in the absence of death receptor stimulation, FADD is found associated to the alpha chain of the nascent polypeptide-associated complex (NAC). Exposure to TNF results in disruption of FADD/NAC complex. Expression of NAC regulates formation of FADD oligomers and modulates FADD-mediated signaling. Thus, our observation indicates that NAC may serve as an intracellular regulator of FADD function.

  18. Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL?

    Directory of Open Access Journals (Sweden)

    Eric J. Niesor

    2015-01-01

    Full Text Available The relationship between levels of high-density lipoprotein cholesterol (HDL-C and cardiovascular (CV risk is well recognized; however, in recent years, large-scale phase III studies with HDL-C-raising or -mimicking agents have failed to demonstrate a clinical benefit on CV outcomes associated with raising HDL-C, casting doubt on the “HDL hypothesis.” This article reviews potential reasons for the observed negative findings with these pharmaceutical compounds, focusing on the paucity of translational models and relevant biomarkers related to HDL metabolism that may have confounded understanding of in vivo mechanisms. A unique function of HDL is its ability to interact with the ATP-binding cassette transporter (ABC A1 via apolipoprotein (Apo A1. Only recently, studies have shown that this process may be involved in the intestinal uptake of dietary sterols and antioxidants (vitamin E, lutein and zeaxanthin at the basolateral surface of enterocytes. This parameter should be assessed for HDL-raising drugs in addition to the more documented reverse cholesterol transport (RCT from peripheral tissues to the liver. Indeed, a single mechanism involving the same interaction between ApoA1 and ABCA1 may encompass two HDL functions previously considered as separate: antioxidant through the intestinal uptake of antioxidants and RCT through cholesterol efflux from loaded cells such as macrophages.

  19. Will Lipidation of ApoA1 through Interaction with ABCA1 at the Intestinal Level Affect the Protective Functions of HDL?

    Science.gov (United States)

    Niesor, Eric J.

    2015-01-01

    The relationship between levels of high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) risk is well recognized; however, in recent years, large-scale phase III studies with HDL-C-raising or -mimicking agents have failed to demonstrate a clinical benefit on CV outcomes associated with raising HDL-C, casting doubt on the “HDL hypothesis.” This article reviews potential reasons for the observed negative findings with these pharmaceutical compounds, focusing on the paucity of translational models and relevant biomarkers related to HDL metabolism that may have confounded understanding of in vivo mechanisms. A unique function of HDL is its ability to interact with the ATP-binding cassette transporter (ABC) A1 via apolipoprotein (Apo) A1. Only recently, studies have shown that this process may be involved in the intestinal uptake of dietary sterols and antioxidants (vitamin E, lutein and zeaxanthin) at the basolateral surface of enterocytes. This parameter should be assessed for HDL-raising drugs in addition to the more documented reverse cholesterol transport (RCT) from peripheral tissues to the liver. Indeed, a single mechanism involving the same interaction between ApoA1 and ABCA1 may encompass two HDL functions previously considered as separate: antioxidant through the intestinal uptake of antioxidants and RCT through cholesterol efflux from loaded cells such as macrophages. PMID:25569858

  20. S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization.

    Science.gov (United States)

    Lee, Mi-Hye; Appleton, Kathryn M; El-Shewy, Hesham M; Sorci-Thomas, Mary G; Thomas, Michael J; Lopes-Virella, Maria F; Luttrell, Louis M; Hammad, Samar M; Klein, Richard L

    2017-02-01

    HDL normally transports about 50-70% of plasma sphingosine 1-phosphate (S1P), and the S1P in HDL reportedly mediates several HDL-associated biological effects and signaling pathways. The HDL receptor, SR-BI, as well as the cell surface receptors for S1P (S1PRs) may be involved partially and/or completely in these HDL-induced processes. Here we investigate the nature of the HDL-stimulated interaction between the HDL receptor, SR-BI, and S1PR1 using a protein-fragment complementation assay and confocal microscopy. In both primary rat aortic vascular smooth muscle cells and HEK293 cells, the S1P content in HDL particles increased intracellular calcium concentration, which was mediated by S1PR1. Mechanistic studies performed in HEK293 cells showed that incubation of cells with HDL led to an increase in the physical interaction between the SR-BI and S1PR1 receptors that mainly occurred on the plasma membrane. Model recombinant HDL (rHDL) particles formed in vitro with S1P incorporated into the particle initiated the internalization of S1PR1, whereas rHDL without supplemented S1P did not, suggesting that S1P transported in HDL can selectively activate S1PR1. In conclusion, these data suggest that S1P in HDL stimulates the transient interaction between SR-BI and S1PRs that can activate S1PRs and induce an elevation in intracellular calcium concentration.

  1. marital status and occupation versus serum total cholesterol and hdl

    African Journals Online (AJOL)

    DR. AMIN

    subjects had higher mean serum TC and HDL – CH levels than male ... MATERIALS AND METHODS ... Fasting various blood (5cm3) sample was collected ... in personal lifestyle and dietary habits of the subjects ... Nutrition 5: 231 – 237.

  2. Cardiac effects of HDL and its components on diabetic cardiomyopathy.

    Science.gov (United States)

    Spillmann, Frank; Van Linthout, Sophie; Tschöpe, Carsten

    2012-06-01

    Diabetic cardiopathy includes a specific cardiomyopathy, which occurs in the absence of coronary heart disease and hypertension under diabetes mellitus. Hyperglycemia, hyperinsulinemia, and hyperlipidemia, characteristic metabolic disturbances evident in diabetes mellitus, all three lead to a specific altered cardiac structure and function. Recently, it has been demonstrated that altered HDL, be it low HDL or dysfunctional HDL is not only a consequence of diabetes mellitus, but can also contribute to the development of diabetes mellitus, and therefore also of diabetic cardiomyopathy. This review summarizes how HDL can indirectly affect diabetic cardiomyopathy via their influence on the metabolic triggers hyperglycemia, hyperinsulinemia, and hyperlipidemia, and how they can directly influence the cardiac cellular consequences, typical for diabetic cardiomyopathy, including inflammation, oxidative stress, apoptosis, fibrosis, Ca2+ handling, glucose homeostasis, and endothelial dysfunction.

  3. You Cannot Live of Love Alone – The Interrelation of Legitimacy and Effectuation in Nascent Markets

    DEFF Research Database (Denmark)

    Günzel-Jensen, Franziska; Rask, Morten

    2015-01-01

    This paper explores how success in legitimacy building can create restrictions and problems for new venture’s development in highly volatile settings. Through a longitudinal single in-depth case study in the nascent e-mobility market, we uncover unwanted effects of this process. In a nascent market...... entrepreneurs need to engage in legitimization activities targeted both at the emerging firm and the emerging industry in which it operates. The gaining of legitimacy from various stakeholders had two consequences: overconfidence which led to misunderstanding of commitment and a lack of learning as well...

  4. Cubilin maintains blood levels of HDL and albumin.

    Science.gov (United States)

    Aseem, Obaidullah; Smith, Brian T; Cooley, Marion A; Wilkerson, Brent A; Argraves, Kelley M; Remaley, Alan T; Argraves, W Scott

    2014-05-01

    Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and apoA-I and significantly increased urinary loss of albumin and apoA-I. Moreover, cubilin HT mice displayed significantly decreased blood levels of albumin, apoA-I, and HDL. The levels of albumin and apoA-I protein or mRNA expressed in the liver, kidney, or intestine of cubilin HT mice did not change significantly. The clearance rate of small HDL3 particles (density>1.13 g/ml) from the blood increased significantly in cubilin HT mice. In contrast, the rate of clearance of larger HDL2 particles from the blood did not change significantly, indicating a decreased half-life for HDL particles capable of filtering through the glomerulus. On the basis of these findings, we conclude that cubilin deficiency reduces renal salvage and delivery back to the blood of albumin and apoA-I, which decreases blood levels of albumin and apoA-I/HDL. These findings raise the possibility that therapeutic increase of renal cubilin expression might reduce proteinuria and increase blood levels of albumin and HDL.

  5. HDL abnormalities in familial hypercholesterolemia: Focus on biological functions.

    Science.gov (United States)

    Ganjali, Shiva; Momtazi, Amir Abbas; Banach, Maciej; Kovanen, Petri T; Stein, Evan A; Sahebkar, Amirhossein

    2017-07-01

    Although a selective strong elevation in the plasma level of low-density lipoprotein (LDL) cholesterol is the hallmark of familial hypercholesterolemia (FH), also other plasma lipoprotein and lipid subspecies are changed in these patients. Several studies in FH patients have pointed to the qualitative abnormalities of high-density lipoprotein (HDL) particles, including their triglyceride and sphingomyelin enrichment, reduced capacity to promote cholesterol efflux from macrophages, impaired anti-inflammatory and anti-oxidant activities, and reduced plasma levels of miRs regulating HDL-dependent cholesterol efflux from macrophage foam cells, typical of atherosclerotic lesions. Thus, accurate understanding of HDL functionality and its disturbances in FH may serve a better estimation of the prognosis and also provide additional clues when searching for novel therapeutic choices in this disease. In spite of such a potential promise, there has been no prior comprehensive review focusing on indices of HDL function in FH patients. In the present review, we aim to fulfill this gap by identifying measures of HDL function that are impaired in FH, and by providing a concise summary on the impact of different lipid-modifying therapies on HDL functionality in FH. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Exposure to High Glucose Concentration Decreases Cell Surface ABCA1 and HDL Biogenesis in Hepatocytes.

    Science.gov (United States)

    Tsujita, Maki; Hossain, Mohammad Anwar; Lu, Rui; Tsuboi, Tomoe; Okumura-Noji, Kuniko; Yokoyama, Shinji

    2017-04-19

    To study atherosclerosis risk in diabetes, we investigated ATP-binding cassette transporter A1 (ABCA1) expression and high-density lipoprotein (HDL) biogenesis in the liver and hepatocytes under hyperglycemic conditions. In streptozotocin-induced diabetic mice, plasma HDL decreased while ABCA1 protein increased without changing its mRNA in the liver, only in the animals that responded to the treatment to show hypoinsulinemia and fasting hyperglycemia but not in the poor responders not showing those. To study the mechanism for this finding, hepatocytes were isolated from the control and diabetic mice, and they showed no difference in expression of ABCA1 protein, its mRNA, and HDL biogenesis in 1 g/l d-glucose but showed decreased HDL biogenesis in 4.5 g/l d-glucose although ABCA1 protein increased without change in its mRNA. Similar findings were confirmed in HepG2 cells with d-glucose but not with l-glucose. Thus, these cell models reproduced the in vivo findings in hyperglycemia. Labeling of cell surface protein revealed that surface ABCA1 decreased in high concentration of d-glucose in HepG2 cells despite the increase of cellular ABCA1 while not with l-glucose. Immunostaining of ABCA1 in HepG2 cells demonstrated the decrease of surface ABCA1 but increase of intracellular ABCA1 with high d-glucose. Clearance of ABCA1 was retarded both in primary hepatocytes and HepG2 cells exposed to high d-glucose but not to l-glucose, being consistent with the decrease of surface ABCA1. It is suggested that localization of ABCA1 to the cell surface is decreased in hepatocytes in hyperglycemic condition to cause decrease of HDL biogenesis.

  7. HDL structure and function is profoundly affected when stored frozen in the absence of cryoprotectants.

    Science.gov (United States)

    Holzer, Michael; Kern, Sabine; Trieb, Markus; Trakaki, Athina; Marsche, Gunther

    2017-09-11

    Analysis of structural and functional parameters of HDL have gained significant momentum in recent years since they are stronger predictors of cardiovascular risk than HDL-cholesterol levels. Surprisingly, in most HDL studies very low attention is paid to HDL storage, which might critically affect functional properties. In the present study, we systematically examined the impact of storage and freezing on structural/functional properties of freshly isolated HDL. Initial damage to HDL starts between week one and four of storage. We observed that prolonged freezing at -20°C or -70°C led to a shedding of apolipoprotein-AI from HDL and to the formation of large protein-poor particles, indicating that HDL is irreversibly disrupted. These structural alterations profoundly affected key metrics of HDL function, including HDL cholesterol efflux capacity and HDL paraoxonase activity. Flash-freezing of isolated HDL prior to storage at -70°C did not preserve HDL structure. However, addition of the cryoprotectants sucrose or glycerol completely preserved structure and function of HDL when stored for at least two years. Our data clearly indicate that HDL is a complex particle requiring special attention when stored. Addition of cryoprotectants to isolated HDL samples before storage will make biochemical and clinical HDL research studies more reproducible and comparable. Copyright © 2017, The American Society for Biochemistry and Molecular Biology.

  8. STUDIES ON THE HDL RECEPTORS I:EVIDENCE FOR THE EXISTENCE OF HDL RECEPTORS IN BEIJING DUCK LIVER

    Institute of Scientific and Technical Information of China (English)

    武须军; 王克勤

    1994-01-01

    It hab been found that Beijing ducks (BD)have a high level of HDL(70%),high LCAT but very low CETP activity and will not develop atheroscletosis on an atherogenic diet,suggesting that cholesterol ester is mainly carried by HDL and metabolized through an HDL receptor pathway in the liver.However,evidence of this recep-tor′s existence in the liver is not yet complete.In this paper,the HDL receptor in BD liver has been studied.Our experiments showed:1)ApoE-free 125I-HDL could bind specifically to duck hepatic cell membrane with high affinity (Kd=9.6 μg/ml)and was saturable(Bmax=8.9μg/mg cell membrane protein)at room temperature.2)Competitive inhibition studies with unlabelled duck,human,rat and chick HDL and duck apo AI and its lipo-somes formed with PC or DMPC could inhibit the binding of 125I-HDL to duck hepatic cell membranes,but LDL,apo Eand their liposomes with PC or DMPC could not with the exception of duck LDL.3)The receptor could rec-ognize apo AI but not apo B or E.4)Both phosphorase A2 and pronase could inhibit the binding activity.The above results give strong evidence for the existence of a specific HLD receptor pathway in the duck liver,support-ing our hypothesis that CE in Beijing ducks is metabolized directly through the hepatic HDL receptor instead of be-ing transfered back to VLDL and LDL,then through the LDL receptor pathway.This unique way of metabolizing CE may be behind the Beijing duck′s antiatherogenicity.

  9. Mechanical modulation of nascent stem cell lineage commitment in tissue engineering scaffolds.

    Science.gov (United States)

    Song, Min Jae; Dean, David; Knothe Tate, Melissa L

    2013-07-01

    Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to stem cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to "map the mechanome", defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates.

  10. Mechanical Modulation of Nascent Stem Cell Lineage Commitment in Tissue Engineering Scaffolds

    Science.gov (United States)

    Song, Min Jae; Dean, David; Tate, Melissa L. Knothe

    2013-01-01

    Taking inspiration from tissue morphogenesis in utero, this study tests the concept of using tissue engineering scaffolds as delivery devices to modulate emergent structure-function relationships at early stages of tissue genesis. We report on the use of a combined computational fluid dynamics (CFD) modeling, advanced manufacturing methods, and experimental fluid mechanics (micro-piv and strain mapping) for the prospective design of tissue engineering scaffold geometries that deliver spatially resolved mechanical cues to cells seeded within. When subjected to a constant magnitude global flow regime, the local scaffold geometry dictates the magnitudes of mechanical stresses and strains experienced by a given cell, and in a spatially resolved fashion, similar to patterning during morphogenesis. In addition, early markers of mesenchymal stem cell lineage commitment relate significantly to the local mechanical environment of the cell. Finally, by plotting the range of stress-strain states for all data corresponding to nascent cell lineage commitment (95% CI), we begin to “map the mechanome”, defining stress-strain states most conducive to targeted cell fates. In sum, we provide a library of reference mechanical cues that can be delivered to cells seeded on tissue engineering scaffolds to guide target tissue phenotypes in a temporally and spatially resolved manner. Knowledge of these effects allows for prospective scaffold design optimization using virtual models prior to prototyping and clinical implementation. Finally, this approach enables the development of next generation scaffolds cum delivery devices for genesis of complex tissues with heterogenous properties, e.g., organs, joints or interface tissues such as growth plates. PMID:23660249

  11. Association Between Paradoxical HDL Cholesterol Decrease and Risk of Major Adverse Cardiovascular Events in Patients Initiated on Statin Treatment in a Primary Care Setting.

    Science.gov (United States)

    Hasvold, Pål; Thuresson, Marcus; Sundström, Johan; Hammar, Niklas; Kjeldsen, Sverre E; Johansson, Gunnar; Holme, Ingar; Bodegård, Johan

    2016-03-01

    Statin-induced changes in high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) are unrelated. Many patients initiated on statins experience a paradoxical decrease in HDL-C. The aim of this study was to evaluate the association between a decrease in HDL-C and risk of major adverse cardiovascular events (MACE). Data from 15,357 primary care patients initiated on statins during 2004-2009 were linked with data from mandatory national hospital, drug-dispensing, and cause-of-death registers, and were grouped according to HDL-C change: decreased ≥0.1 mmol/L, unchanged ±0.1 or ≥0.1 mmol/L increased. To evaluate the association between decrease in HDL-C and risk of MACE, a sample of propensity score-matched patients from the decreased and unchanged groups was created, using the latter group as reference. MACE was defined as myocardial infarction, unstable angina pectoris, ischaemic stroke, or cardiovascular mortality. Cox proportional hazards models were used to estimate relative risks. HDL-C decreased in 20%, was unchanged in 58%, and increased in 22% of patients initiated on statin treatment (96% treated with simvastatin). The propensity score-matched sample comprised 5950 patients with mean baseline HDL-C and LDL-C of 1.69 and 4.53 mmol/L, respectively. HDL-C decrease was associated with 56% higher MACE risk (hazard ratio 1.56; 95% confidence interval 1.12-2.16; p < 0.01) compared with the unchanged HDL-C group. Paradoxical statin-induced reduction in HDL-C was relatively common and was associated with increased risk of MACE.

  12. Nascent ventures competing for start-up capital: matching reputations and investors

    NARCIS (Netherlands)

    Ebbers, J.J.; Wijnberg, N.M.

    2012-01-01

    Although nascent ventures have not yet developed a performance-based reputation, the individual reputations of their founders, based on the performance of their earlier ventures, can function as important signals to investors. Selection system theory distinguishes between different types of reputati

  13. Nascent chromatin capture proteomics determines chromatin dynamics during DNA replication and identifies unknown fork components

    DEFF Research Database (Denmark)

    Alabert, Constance; Bukowski-Wills, Jimi-Carlo; Lee, Sung-Po

    2014-01-01

    To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use nascent chromatin capture (NCC) to profile chromatin proteome dynamics durin...

  14. Dissecting the nascent human transcriptome by analysing the RNA content of transcription factories

    Science.gov (United States)

    Caudron-Herger, Maïwen; Cook, Peter R.; Rippe, Karsten; Papantonis, Argyris

    2015-01-01

    While mapping total and poly-adenylated human transcriptomes has now become routine, characterizing nascent transcripts remains challenging, largely because nascent RNAs have such short half-lives. Here, we describe a simple, fast and cost-effective method to isolate RNA associated with transcription factories, the sites responsible for the majority of nuclear transcription. Following stimulation of human endothelial cells with the pro-inflammatory cytokine TNFα, we isolate and analyse the RNA content of factories by sequencing. Comparison with total, poly(A)+ and chromatin RNA fractions reveals that sequencing of purified factory RNA maps the complete nascent transcriptome; it is rich in intronic unprocessed transcript, as well as long intergenic non-coding (lincRNAs) and enhancer-associated RNAs (eRNAs), micro-RNA precursors and repeat-derived RNAs. Hence, we verify that transcription factories produce most nascent RNA and confer a regulatory role via their association with a set of specifically-retained non-coding transcripts. PMID:25897132

  15. The effect of human capital, social capital, and perceptual values on nascent entrepreneurs' export intentions

    DEFF Research Database (Denmark)

    Christensen, Poul Rind; Evald, Majbritt Rostgaard; Klyver, Kim

    2011-01-01

    This study investigates the influence of human capital, social capital, and cognition on nascent entrepreneurs' export intentions. The results indicate that while human capital and social capital influence the level of intended export, cognitive characteristics, such as self-efficacy and risk...

  16. Chromatin Dynamics During DNA Replication and Uncharacterized Replication Factors determined by Nascent Chromatin Capture (NCC) Proteomics

    Science.gov (United States)

    Alabert, Constance; Bukowski-Wills, Jimi-Carlo; Lee, Sung-Bau; Kustatscher, Georg; Nakamura, Kyosuke; de Lima Alves, Flavia; Menard, Patrice; Mejlvang, Jakob; Rappsilber, Juri; Groth, Anja

    2014-01-01

    SUMMARY To maintain genome function and stability, DNA sequence and its organization into chromatin must be duplicated during cell division. Understanding how entire chromosomes are copied remains a major challenge. Here, we use Nascent Chromatin Capture (NCC) to profile chromatin proteome dynamics during replication in human cells. NCC relies on biotin-dUTP labelling of replicating DNA, affinity-purification and quantitative proteomics. Comparing nascent chromatin with mature post-replicative chromatin, we provide association dynamics for 3995 proteins. The replication machinery and 485 chromatin factors like CAF-1, DNMT1, SUV39h1 are enriched in nascent chromatin, whereas 170 factors including histone H1, DNMT3, MBD1-3 and PRC1 show delayed association. This correlates with H4K5K12diAc removal and H3K9me1 accumulation, while H3K27me3 and H3K9me3 remain unchanged. Finally, we combine NCC enrichment with experimentally derived chromatin probabilities to predict a function in nascent chromatin for 93 uncharacterized proteins and identify FAM111A as a replication factor required for PCNA loading. Together, this provides an extensive resource to understand genome and epigenome maintenance. PMID:24561620

  17. Evaluation of CETP activity in vivo under non-steady-state conditions: influence of anacetrapib on HDL-TG flux.

    Science.gov (United States)

    McLaren, David G; Previs, Stephen F; Phair, Robert D; Stout, Steven J; Xie, Dan; Chen, Ying; Salituro, Gino M; Xu, Suoyu S; Castro-Perez, Jose M; Opiteck, Gregory J; Akinsanya, Karen O; Cleary, Michele A; Dansky, Hayes M; Johns, Douglas G; Roddy, Thomas P

    2016-03-01

    Studies in lipoprotein kinetics almost exclusively rely on steady-state approaches to modeling. Herein, we have used a non-steady-state experimental design to examine the role of cholesteryl ester transfer protein (CETP) in mediating HDL-TG flux in vivo in rhesus macaques, and therefore, we developed an alternative strategy to model the data. Two isotopomers ([(2)H11] and [(13)C18]) of oleic acid were administered (orally and intravenously, respectively) to serve as precursors for labeling TGs in apoB-containing lipoproteins. The flux of a specific TG (52:2) from these donor lipoproteins to HDL was used as the measure of CETP activity; calculations are also presented to estimate total HDL-TG flux. Based on our data, we estimate that the peak total postprandial TG flux to HDL via CETP is ∼ 13 mg · h(-1) · kg(-1) and show that this transfer was inhibited by 97% following anacetrapib treatment. Collectively, these data demonstrate that HDL TG flux can be used as a measure of CETP activity in vivo. The fact that the donor lipoproteins can be labeled in situ using well-established stable isotope tracer techniques suggests ways to measure this activity for native lipoproteins in free-living subjects under any physiological conditions. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  18. Low HDL Cholesterol and the Risk of Diabetic Nephropathy and Retinopathy Results of the ADVANCE study

    NARCIS (Netherlands)

    Morton, Jamie; Zoungas, Sophia; Li, Qiang; Patel, Anushka A.; Chalmers, John; Woodward, Mark; Celermajer, David S.; Beulens, Joline W. J.; Stolk, Ronald P.; Glasziou, Paul; Ng, Martin K. C.

    2012-01-01

    OBJECTIVE-Although low HDL cholesterol (HDL-C) is an established risk factor for atherosclerosis, data on HDL-C and the risk of microvascular disease are limited. We tested the association between HDL-C and microvascular disease in a cohort of patients with type 2 diabetes. RESEARCH DESIGN AND

  19. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    Science.gov (United States)

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C l...

  20. Correlation between Ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C with the Severity of Coronary Heart Disease%TC/HDL-C、LDL-C/HDL-C、TG/HDL-C与冠心病不同程度相关性

    Institute of Scientific and Technical Information of China (English)

    吴燕丹

    2014-01-01

    Objective To explore predictive values of ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C of pa-tients with coronary heart disease ( CHD) for condition severity. Methods A total of 175 CHD patients undergoing coronary artery stent placement were recruited as CHD group, and 146 heatlhy persons taking physical examination without cardiovascu-lar disease were chosen as control group. Seven parts of blood lipids indexes [ total cholesterol ( TC) , triglyceride ( TG) , low density lipoprotein cholesterol ( LDL-C) , high density lipoprotein cholesferol ( HDL-C) , ratios of TC/HDL-C, LDL-C/HDL-C and TG/HDL-C] were detected in the two groups. The differences of the indexes in the two groups and value changes of blood lipids in different lesions (3 lesions, 2 lesions and 1 lesion) were analyzed, and the correlations between the indexes and changes in different lesions were also analyzed. Results The seven indexes in CHD group were significantly higher than those in control group ( P<0.01 ); ratios of TC/HDL-C and TG/HDL-C in patients with 3 lesions were significantly higher than those in patients with 2 lesions or 1 lesion (P<0.05);ratios of TC/HDL-C and LDL-C/HDL-C in patients with 3 or 2 lesions were significantly higher than those in patients with 1 lesion ( P<0.05 ); HDL-C ratio in patients with 3 lesions was significantly lower than that in patients with 1 lesion (P<0.05). Conclusion The blood lipids ratios are closely related to lesion numbers in patients with coronary heart disease. So it can be used as routine index in prediction of CHD conditions.%目的探讨冠心病患者血清总胆固醇( TC )/高密度脂蛋白胆固醇( HDL-C )、低密度脂蛋白胆固醇( LDL-C)/HDL-C、甘油三酯( TG)/HDL-C比值对病情严重程度的预测价值。方法选择明确诊断为冠心病并放置冠状动脉(冠脉)支架的175例作为冠心病组,选择同期无心血管疾病的健康体检者146例作为对照组。冠心病组及对照组均测定血脂7项,即TC

  1. The exosome associates cotranscriptionally with the nascent pre-mRNP through interactions with heterogeneous nuclear ribonucleoproteins

    DEFF Research Database (Denmark)

    Hessle, Viktoria; Björk, Petra; Sokolowski, Marcus

    2009-01-01

    Eukaryotic cells have evolved quality control mechanisms to degrade aberrant mRNA molecules and prevent the synthesis of defective proteins that could be deleterious for the cell. The exosome, a protein complex with ribonuclease activity, is a key player in quality control. An early quality...... checkpoint takes place cotranscriptionally but little is known about the molecular mechanisms by which the exosome is recruited to the transcribed genes. Here we study the core exosome subunit Rrp4 in two insect model systems, Chironomus and Drosophila. We show that a significant fraction of Rrp4...... is associated with the nascent pre-mRNPs and that a specific mRNA-binding protein, Hrp59/hnRNP M, interacts in vivo with multiple exosome subunits. Depletion of Hrp59 by RNA interference reduces the levels of Rrp4 at transcription sites, which suggests that Hrp59 is needed for the exosome to stably interact...

  2. Pitavastatin and HDL: Effects on plasma levels and function(s).

    Science.gov (United States)

    Pirillo, Angela; Catapano, Alberico L

    2017-07-01

    Low high density lipoprotein cholesterol (HDL-C) levels represent an independent risk factor for cardiovascular disease; in addition to the reduced HDL-C levels commonly observed in patients at cardiovascular risk, the presence of dysfunctional HDL, i.e. HDL with reduced atheroprotective properties, has been reported. Despite the established inverse correlation between HDL-C levels and cardiovascular risk, several clinical trials with HDL-C-increasing drugs (such as niacin, CETP inhibitors or fibrate) failed to demonstrate that a significant rise in HDL-C levels translate into a cardiovascular benefit. Statins, that are the most used lipid-lowering drugs, can also increase HDL-C levels, although this effect is highly variable among studies and statins; the most recent developed statin, pitavastatin, beside its role as LDL-C-lowering agent, increases HDL-C levels at a significantly higher extent and progressively upon treatment; such increase was observed also when patients where shifted from another statin to pitavastatin. The stratification by baseline HDL-C levels revealed that only pitavastatin significantly increased HDL-C levels in patients with baseline HDL-C ≤45 mg/dl, while no changes were observed in patients with higher baseline HDL-C levels. In the last years the hypothesis that functional properties of HDL may be more relevant than HDL-C levels has risen from several observations. The treatment with pitavastatin not only increased HDL-C levels, but also increased the phospholipid content of HDL, increased the HDL efflux capacity and their anti-oxidant properties. These observations suggest that, besides its high LDL-C-lowering effect, pitavastatin also exhibits a significantly higher ability to increase HDL-C levels and may also positively affect the quality and functionality of HDL particles. Copyright © 2017 Elsevier B.V. All rights reserved.

  3. HDL2-C和HDL3-C与老年男性冠心病发病相关性分析%Correlation analysis of high-density lipoprotein subfractions(HDL2,HDL3)and coronary heart disease in the male elderly

    Institute of Scientific and Technical Information of China (English)

    赵勇; 任红旗; 史跃; 项军

    2012-01-01

    目的 探讨高密度脂蛋白胆固醇亚组分(HDL2-C和HDL3-C)与老年男性冠心病发病相关性.方法 随机选择老年男性冠心病60例,无冠心病老年男性60例为对照组.应用硫酸葡聚糖-镁法测定HDL-C亚组分HDL2-C和HDL3-C,并分析其与冠心病发生的相关性.结果 与对照组相比,老年男性冠心病组HDL-C和HDL3-C均显著下降(P均0.05).Logistic回归分析显示HDL3-C、低密度脂蛋白胆固醇(LDL-C)、糖化血红蛋白(HbA1c)及高血压病作为老年男性冠心病发病的独立危险因子进入回归方程,HDL-C和HDL2-C未进入方程.Spearman秩相关分析显示HDL3-C与冠心病发病的负相关性(r=-0.310,P=0.030)优于HDL-C(r=-0.154,P=0.274)和HDL2-C(r=-0.014,P=0.924).结论 HDL3-C与老年男性冠心病发病的负相关性优于HDL-C和HDL2-C,HDL3-C是老年男性冠心病发生的独立危险因子,HDL-C抗冠状动脉粥样硬化作用可能主要是通过HDL3-C实现的.%Objective To evaluate whether one or both of the major high-density lipoprotein ( HDL) subfractions ( HDL2, HDL3 ) is associated with the risk of coronary heart disease ( CHD ) in the male elderly. Methods Sixty people with CHD were randomly selected as group A and 60 people without CHD as the control , all the examinations were the male elderly. The separation of HDL subfractions was carried out by dextran sulfate -magnesium chloride technique , and the correlation between HDL subfractions ( HDL2, HDL3 ) and coronary heart disease were analyzed. Results The group A had significantly lower HDL and HDL 3 cholesterol levels compared to the control ( both P < 0. 01 ) , while HDL2 cholesterol levels was not significantly reduced . The Spearman rank correlation analysis indicated that CHD significantly correlated with HDL 3 cholesterol (r = - 0. 310 , P = 0. 030 ) , but not with HDL cholesterol ( r = - 0. 154, P = 0. 274 ) and HDL2 cholesterol ( r = - 0. 014 , P = 0. 924 ). Logistic regression analysis revealed that HDL3

  4. The inverse association of serum HBV DNA level with HDL and adiponectin in chronic hepatitis B infection

    Directory of Open Access Journals (Sweden)

    Mohamadkhani Ashraf

    2010-09-01

    Full Text Available Abstract BACKGROUND The natural history of hepatitis B virus (HBV is complex and influenced by the level of viral replication and host factors. The hepatoprotective role of high density lipoproteins (HDL and adiponectin as host factors on HBV persistence is less well understood. METHODS To investigate correlation between HBV DNA level with clinical parameters in patients with chronic hepatitis B, 92 male subjects with HBV infection without any risk factors for diabetes were enrolled in this study. Age and BMI of the study population were matched and HBV DNA, ALT, tumor necrosis factor alpha (TNF-α, adiponectin and lipid levels was measured. RESULTS Serum HBV DNA correlated inversely with serum HDL level (r = -0.23; P = 0.014. The median of log copies/ml for HBV DNA (3.67 was considered as cut off point. Patients with HBV DNA level higher than cut off point had lower adiponectin (8.7 ± 5.3 vs 10.7 ± 4.9 μg/ml p = 0.05. Also, adiponectin had a negative correlation with TNF-α (r = -0.21, P = 0.04 and positive correlations with HDL (r = 0.18, P = 0.043.Multivariate regression models show that serum HDL level is an independed factor to predict serum HBV DNA. CONCLUSION Our findings showed that higher HBV DNA levels are associated with lower HDL and adiponectin but induced TNF-alpha values.

  5. Facilitating Employees' and Students' Process towards Nascent Entrepreneurship

    Science.gov (United States)

    Hietanen, Lenita

    2015-01-01

    Purpose: The purpose of this paper is to investigate a model for facilitating employees' and full-time, non-business students' entrepreneurial capabilities during their optional entrepreneurship studies at one Finnish Open University. Design/methodology/approach: The case study investigates the course in which transitions from employees or…

  6. Facilitating Employees' and Students' Process towards Nascent Entrepreneurship

    Science.gov (United States)

    Hietanen, Lenita

    2015-01-01

    Purpose: The purpose of this paper is to investigate a model for facilitating employees' and full-time, non-business students' entrepreneurial capabilities during their optional entrepreneurship studies at one Finnish Open University. Design/methodology/approach: The case study investigates the course in which transitions from employees or…

  7. Design and Co-Simulation of Depth Estimation Using Simulink HDL Coder and Modelsim

    Directory of Open Access Journals (Sweden)

    FARIDA MEMON

    2016-07-01

    Full Text Available In this paper a novel VHDL design procedure of depth estimation algorithm using HDL (Hardware Description Language Coder is presented. A framework is developed that takes depth estimation algorithm described in MATLAB as input and generates VHDL code, which dramatically decreases the time required to implement an application on FPGAs (Field Programmable Gate Arrays. In the first phase, design is carriedout in MATLAB. Using HDL Coder, MATLAB floating- point design is converted to an efficient fixed-point design and generated VHDL Code and test-bench from fixed point MATLAB code. Further, the generated VHDL code of design is verified with co-simulation using Mentor Graphic ModelSim10.3d software. Simulation results are presented which indicate that VHDL simulations match with the MATLAB simulations and confirm the efficiency of presented methodology.

  8. Changes in apolipoprotein E-containing high-density lipoprotein (HDL) have little impact on HDL-cholesterol measurements using homogeneous assays in normolipidemic and dyslipidemic subjects.

    Science.gov (United States)

    Sasamoto, Kenta; Hirayama, Satoshi; Kon, Mika; Seino, Utako; Ueno, Tsuyoshi; Nagao, Yuki; Hirayama, Akiko; Isshiki, Miwa; Idei, Mayumi; Yano, Kouji; Miida, Takashi

    2017-07-01

    High-density lipoprotein-cholesterol (HDL-C) is generally measured using several homogeneous assays. We aimed to clarify whether apolipoprotein E-containing HDL (apoE-HDL) subfractions are altered during storage, and if so, whether such changes affect the HDL-C concentration measured using homogeneous assays. We stored serum from normolipidemic (n=32) and dyslipidemic (n=17) subjects at 4°C for up to 7days. ApoE-HDL subfractions were analyzed using native 2-dimensional gel (native 2D-gel) electrophoresis. HDL-C concentrations were determined using 2 precipitation and 4homogeneous assays. Native 2D-gel electrophoresis revealed variously sized apoE-HDL subfractions. After 4h incubation at 37°C, subfractions of smaller particles were converted into larger particles by lecithin:cholesterol acyltransferase (LCAT) activity. After 7days storage at 4°C, the smaller subfractions were decreased in the normolipidemic group, accompanying increases in larger subfractions, whereas changes in the respective subfractions varied among individuals in the dyslipidemic group. HDL-C concentrations were significantly lower after storage at 4°C in all assays, except that using Sekisui Medical's reagent. Therefore, changes in HDL-C concentration and apoE-HDL subfractions were independent of each other. ApoE-HDL subfractions change during storage, but these changes are not linked to those in HDL-C concentration measured using homogeneous assays. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. Role of HDL cholesterol and estimates of HDL particle composition in future development of type 2 diabetes in the general population : the PREVEND study

    NARCIS (Netherlands)

    Abbasi, Ali; Corpeleijn, Eva; Gansevoort, Ron T.; Gans, Rijk O. B.; Hillege, Hans L.; Stolk, Ronald P.; Navis, Gerjan; Bakker, Stephan J. L.; Dullaart, Robin P. F.

    Background and Aims: High-density lipoproteins (HDLs) may directly stimulate beta-cell function and glucose metabolism. We determined the relationships of fasting high-density lipoprotein cholesterol (HDL-C), plasma apolipoprotein (apo) A-I and apoA-II, and HDL-C-to-apoA-I and HDL-C-to-apoA-II

  10. Volumetric determination of apolipoprotein stoichiometry of circulating HDL subspecies1[S

    Science.gov (United States)

    Segrest, Jere P.; Cheung, Marian C.; Jones, Martin K.

    2013-01-01

    Although HDL is inversely correlated with coronary heart disease, elevated HDL-cholesterol is not always protective. Additionally, HDL has biological functions that transcend any antiatherogenic role: shotgun proteomics show that HDL particles contain 84 proteins (latest count), many correlating with antioxidant and anti-inflammatory properties of HDL. ApoA-I has been suggested to serve as a platform for the assembly of these protein components on HDL with specific functions - the HDL proteome. However, the stoichiometry of apoA-I in HDL subspecies is poorly understood. Here we use a combination of immunoaffinity chromatography data and volumetric analysis to evaluate the size and stoichiometry of LpA-I and LpA-I,A-II particles. We conclude that there are three major LpA-I subspecies: two major particles, HDL[4] in the HDL3 size range (d = 85.0 ± 1.2 Å) and HDL[7] in the HDL2 size range (d = 108.5 ± 3.8 Å) with apoA-I stoichiometries of 3 and 4, respectively, and a small minor particle, HDL[1] (d = 73.8 ± 2.1Å) with an apoA-I stoichiometry of 2. Additionally, we conclude that the molar ratio of apolipoprotein to surface lipid is significantly higher in circulating HDL subspecies than in reconstituted spherical HDL particles, presumably reflecting a lack of phospholipid transfer protein in reconstitution protocols. PMID:23883582

  11. Thermal transitions in serum amyloid A in solution and on the lipid: implications for structure and stability of acute-phase HDL[S

    Science.gov (United States)

    Jayaraman, Shobini; Haupt, Christian; Gursky, Olga

    2015-01-01

    Serum amyloid A (SAA) is an acute-phase protein that circulates mainly on plasma HDL. SAA interactions with its functional ligands and its pathogenic deposition in reactive amyloidosis depend, in part, on the structural disorder of this protein and its propensity to oligomerize. In vivo, SAA can displace a substantial fraction of the major HDL protein, apoA-I, and thereby influence the structural remodeling and functions of acute-phase HDL in ways that are incompletely understood. We use murine SAA1.1 to report the first structural stability study of human plasma HDL that has been enriched with SAA. Calorimetric and spectroscopic analyses of these and other SAA-lipid systems reveal two surprising findings. First, progressive displacement of the exchangeable fraction of apoA-I by SAA has little effect on the structural stability of HDL and its fusion and release of core lipids. Consequently, the major determinant for HDL stability is the nonexchangeable apoA-I. A structural model explaining this observation is proposed, which is consistent with functional studies in acute-phase HDL. Second, we report an α-helix folding/unfolding transition in SAA in the presence of lipid at near-physiological temperatures. This new transition may have potentially important implications for normal functions of SAA and its pathogenic misfolding. PMID:26022803

  12. 基于Simulink HDL Coder的跳频通信系统设计与实现%Design and Implementation of Frequency Hopping Communication System Based on Simulink HDL Coder

    Institute of Scientific and Technical Information of China (English)

    杜广超; 孙慧慧; 杨云升; 杨志飞

    2016-01-01

    In the FPGA development, the model⁃based method is fewer applied. A frequency hopping communication system is designed based on simulink model.The simulink simulation model of frequency hopping communication system is transformed to HDL code by simulink HDL Coder.The bit file,which is built in ISE,is then loaded into FPGA.At last,real⁃time voice communication is realized on the FPGA signal processing board.The merits and demerits of this method to realize FPGA algorithm based on simulink mod⁃el are analyzed,which is of a certain guiding value to the FPGA development and the extended application of simulink HDL Coder.%针对目前FPGA程序开发中模型开发方式应用较少的现状,基于simulink模型设计了跳频通信系统,利用simulink HDL Coder将跳频通信系统simulink仿真模型转换为HDL 代码,在 ISE 中编译生成 bit 文件后加载到 FPGA 芯片之中,在FPGA信号处理板上实现了话音的实时通信。对基于 simulink 模型实现 FPGA 算法方法的优缺点进行了分析,对FPGA算法开发实现和simulink HDL Coder的推广应用具有一定的指导意义。

  13. Cubilin Maintains Blood Levels of HDL and Albumin

    OpenAIRE

    Aseem, Obaidullah; Smith, Brian T; Cooley, Marion A.; Wilkerson, Brent A.; Argraves, Kelley M.; Remaley, Alan T.; Argraves, W Scott

    2013-01-01

    Cubilin is an endocytic receptor highly expressed in renal proximal tubules, where it mediates uptake of albumin and filtered forms of apoA-I/HDL. Cubilin deficiency leads to urinary loss of albumin and apoA-I; however, the consequences of cubilin loss on the homeostasis of blood albumin and apoA-I/HDL have not been studied. Using mice heterozygous for cubilin gene deletion (cubilin HT mice), we show that cubilin haploinsufficiency leads to reduced renal proximal tubular uptake of albumin and...

  14. Candidate exoplanet host HD 131399A: a nascent Am star

    Science.gov (United States)

    Przybilla, N.; Aschenbrenner, P.; Buder, S.

    2017-08-01

    Direct imaging suggests that there is a Jovian exoplanet around the primary A-star in the triple-star system HD 131399. We investigate a high-quality spectrum of the primary component HD 131399A obtained with FEROS on the ESO/MPG 2.2 m telescope, aiming to characterise the star's atmospheric and fundamental parameters, and to determine elemental abundances at high precision and accuracy. The aim is to constrain the chemical composition of the birth cloud of the system and therefore the bulk composition of the putative planet. A hybrid non-local thermal equilibrium (non-LTE) model atmosphere technique is adopted for the quantitative spectral analysis. Comparison with the most recent stellar evolution models yields the fundamental parameters. The atmospheric and fundamental stellar parameters of HD 131399A are constrained to Teff = 9200 ± 100 K, log g = 4.37 ± 0.10, , , and log L/L⊙ = 1.17 ± 0.07, locating the star on the zero-age main sequence. Non-LTE effects on the derived metal abundances are often smaller than 0.1 dex, but can reach up to 0.8 dex for individual lines. The observed lighter elements up to calcium are overall consistent with present-day cosmic abundances, with a C/O ratio of 0.45 ± 0.07 by number, while the heavier elements show mild overabundances. We conclude that the birth cloud of the system had a standard chemical composition, but we witness the onset of the Am phenomenon in the slowly rotating star. We furthermore show that non-LTE analyses have the potential to solve the remaining discrepancies between observed abundances and predictions by diffusion models for Am stars. Moreover, the present case allows mass loss, not turbulent mixing, to be identified as the main transport process competing with diffusion in very young Am stars.

  15. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications.

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction.

  16. HDL-S1P: cardiovascular functions, disease-associated alterations, and therapeutic applications

    Science.gov (United States)

    Levkau, Bodo

    2015-01-01

    Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid contained in High-density lipoproteins (HDL) and has drawn considerable attention in the lipoprotein field as numerous studies have demonstrated its contribution to several functions inherent to HDL. Some of them are partly and some entirely due to the S1P contained in HDL (HDL-S1P). Despite the presence of over 1000 different lipids in HDL, S1P stands out as it possesses its own cell surface receptors through which it exercises key physiological functions. Most of the S1P in human plasma is associated with HDL, and the amount of HDL-S1P influences the quality and quantity of HDL-dependent functions. The main binding partner of S1P in HDL is apolipoprotein M but others may also exist particularly under conditions of acute S1P elevations. HDL not only exercise functions through their S1P content but have also an impact on genuine S1P signaling by influencing S1P bioactivity and receptor presentation. HDL-S1P content is altered in human diseases such as atherosclerosis, coronary artery disease, myocardial infarction, renal insufficiency and diabetes mellitus. Low HDL-S1P has also been linked to impaired HDL functions associated with these disorders. Although the pathophysiological and molecular reasons for such disease-associated shifts in HDL-S1P are little understood, there have been successful approaches to circumvent their adverse implications by pharmacologically increasing HDL-S1P as means to improve HDL function. This mini-review will cover the current understanding of the contribution of HDL-S1P to physiological HDL function, its alteration in disease and ways for its restoration to correct HDL dysfunction. PMID:26539121

  17. Static Calibration and Analysis of the Velodyne HDL-64E S2 for High Accuracy Mobile Scanning

    OpenAIRE

    Craig Glennie; Lichti, Derek D.

    2010-01-01

    The static calibration and analysis of the Velodyne HDL-64E S2 scanning LiDAR system is presented and analyzed. The mathematical model for measurements for the HDL-64E S2 scanner is derived and discussed. A planar feature based least squares adjustment approach is presented and utilized in a minimally constrained network in order to derive an optimal solution for the laser’s internal calibration parameters. Finally, the results of the adjustment along with a detailed examination of the adjust...

  18. HIV-infected patients show functionally defective high-density lipoprotein (HDL paralleled with changes in HDL-associated proteins

    Directory of Open Access Journals (Sweden)

    V Estrada

    2012-11-01

    Full Text Available Purpose of the study Epidemiological studies have consistently demonstrated an inverse association between plasma HDL concentrations and cardiovascular risk. Although this cardioprotective role has been mainly attributed to its role in promoting cellular cholesterol efflux, there is an emerging interest in the anti-inflammatory and antioxidant properties of HDL. The aim of the study is to investigate the anti-inflammatory properties of HDL isolated from HIV-infected patients. Methods Cross-sectional study of 113 HIV-infected patients and 70 non-infected control subjects without evident CVD. From each subject, HDL was isolated by ultracentrifugation and its anti-inflammatory status was tested as its ability to inhibit MCP-1-induced migration of the monocytic cell line THP-1 using transwell cell culture chamber inserts with micropore filters of 5 microns pore size. HDL-associated proteins were measured by commercial ELISAs. Results Twenty-three HIV-infected patients were ART-naïve (32±15 years, 66.7% male and ninety were currently on ART (46±11 years, 78.9 % male. Most patients on ART (91.1% had undetectable viral load (<50 copies/mL. When compared to healthy subjects, both naïve and treated HIV-infected patients had lower plasma HDL-cholesterol levels (naïve: 45±12, ART: 50±10, controls: 55±10 mg/dL, p<0.05. HDL isolated from HIV naïve patients showed a significantly reduced anti-inflammatory activity (THP-1 monocyte migration capacity was 203% times higher in HIV patients than in control subjects. The anti-inflammatory activity of HDL from ART-treated HIV-infected patients was significantly improved when compared to naïve patients, although it remained significantly lower than controls (130% THP-1 monocyte migration vs controls. HDL from HIV-infected patients had a decreased concentration of the anti-inflammatory proteins Apo A1 (controls: 2.1±0.3, naïve: 1.4±0.2, ART: 1.6±0.1 mg/ml and LCAT (controls: 0.53±0.09, naïve: 0.34±0

  19. 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.

  20. Learning Entrepreneurial Leadership among Nascent Food Entrepreneurs in Denmark and New Zealand

    DEFF Research Database (Denmark)

    Ramsgaard, Michael Breum; Warren, Lorraine

    2015-01-01

    in the nascent phases. We analyse the factors constituting the processes of learning entrepreneurial leadership among nascent food entrepreneurs. The primary source of data derives from four in-depth interviews in each country with founders of SME food businesses with no more than 5 years of company history......This paper examines the process of learning entrepreneurial leadership in small food businesses in the early stages. It draws on the growing body of research around entrepreneurial leadership that deals with leadership in ventures but overlooks the importance of entrepreneurial leadership....... Further we discuss whether regional differences in the conception of entrepreneurial leadership can be identified through comparison between qualitative data from Denmark and New Zealand....

  1. Effect of Nascent Peptide Steric Bulk on Elongation Kinetics in the Ribosome Exit Tunnel.

    Science.gov (United States)

    Po, Pengse; Delaney, Erin; Gamper, Howard; Szantai-Kis, D Miklos; Speight, Lee; Tu, LiWei; Kosolapov, Andrey; Petersson, E James; Hou, Ya-Ming; Deutsch, Carol

    2017-06-16

    All proteins are synthesized by the ribosome, a macromolecular complex that accomplishes the life-sustaining tasks of faithfully decoding mRNA and catalyzing peptide bond formation at the peptidyl transferase center (PTC). The ribosome has evolved an exit tunnel to host the elongating new peptide, protect it from proteolytic digestion, and guide its emergence. It is here that the nascent chain begins to fold. This folding process depends on the rate of translation at the PTC. We report here that besides PTC events, translation kinetics depend on steric constraints on nascent peptide side chains and that confined movements of cramped side chains within and through the tunnel fine-tune elongation rates. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Nascent peptide side chains induce rearrangements in distinct locations of the ribosomal tunnel.

    Science.gov (United States)

    Lu, Jianli; Hua, Zhengmao; Kobertz, William R; Deutsch, Carol

    2011-08-12

    Although we have numerous structures of ribosomes, none disclose side-chain rearrangements of the nascent peptide during chain elongation. This study reports for the first time that rearrangement of the peptide and/or tunnel occurs in distinct regions of the tunnel and is directed by the unique primary sequence of each nascent peptide. In the tunnel mid-region, the accessibility of an introduced cysteine to a series of novel hydrophilic maleimide reagents increases with increasing volume of the adjacent chain residue, a sensitivity not manifest at the constriction and exit port. This surprising result reveals molecular movements not yet resolvable from structural studies. These findings map solvent-accessible volumes along the tunnel and provide novel insights critical to our understanding of allosteric communication within the ribosomal tunnel, translational arrest, chaperone interaction, folding, and rates of elongation.

  3. Purification of Messenger Ribonucleoprotein Particles via a Tagged Nascent Polypeptide.

    Directory of Open Access Journals (Sweden)

    Diana P Inchaustegui Gil

    Full Text Available The cytoplasmic fates of mRNAs are influenced by interactions between RNA-binding proteins and cis regulatory motifs. In the cytoplasm, mRNAs are present as messenger ribonucleoprotein particles, which include not only proteins that bind directly to the mRNA, but also additional proteins that are recruited via protein-protein interactions. Many labs have sought to purify such particles from cells, with limited success. We here describe a simple two-step procedure to purify actively translated mRNAs, with their associated proteins, from polysomes. We use a reporter mRNA that encodes a protein with three streptavidin binding peptides at the N-terminus. The polysomal reporter mRNA, with associated proteins, is purified via binding to a streptavidin matrix. The method takes four days, and can be applied in any cell that can be genetically manipulated. Using Trypanosoma brucei as a model system, we routinely purified 8% of the input reporter mRNA, with roughly 22-fold enrichment relative to un-tagged mRNAs, a final reporter-mRNA:total-mRNA ratio of about 1:10, and a protein purification factor of slightly over 1000-fold. Although the overall reporter mRNP composition is masked by the presence of proteins that are associated with many polysomal mRNAs, our method can be used to detect association of an RNA-binding protein that binds to specifically to a reporter mRNA.

  4. The mouse QTL map helps interpret human genome-wide association studies for HDL cholesterol.

    Science.gov (United States)

    Leduc, Magalie S; Lyons, Malcolm; Darvishi, Katayoon; Walsh, Kenneth; Sheehan, Susan; Amend, Sarah; Cox, Allison; Orho-Melander, Marju; Kathiresan, Sekar; Paigen, Beverly; Korstanje, Ron

    2011-06-01

    Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies.

  5. 胰岛素抵抗稳态模式评估与LDL-C/HDL-C和TC/HDL-C比值测定关系的探讨

    Institute of Scientific and Technical Information of China (English)

    孟立辉; 李景平; 王宣; 岳晓亮

    2011-01-01

    目的 评价胰岛素抵抗稳态模式评估胰岛素抵抗指数(HOMA-IR)与LDL-C/HDL-C和TC/HDL-C比值测定的关系.方测定正常糖耐量(NGT)组、糖耐量受损(IGT)组和2型糖尿病(MD)组,空腹血糖(FPG)、空腹胰岛素(FINS)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C).计算稳态模式评估胰岛素抵抗指数(HOMA-IR)和LDL-C/HDL-C和TC/HDL-C比值.结果 IGT组、DM组与NGT组比较,HOMA-IR、LDL-C/HDL-C、TC/HDL-C均有较显著的统计学差异(P<0.01),其值明显升高,并且HOMA-IR与LDL-C/HDL-C和TC/HDL-C比值测定有一定的相关性.结论 我们认为联合测定胰岛素抵抗指数(HOMA-IR)和LDL-C/HDL-C、TC/HDL-C比值,可作为胰岛素抵抗较好的诊断及治疗指标.

  6. Varieties of semi-presidentialism and their impact on nascent democracies

    OpenAIRE

    Elgie, Robert

    2007-01-01

    Semi-presidentialism is the situation where the constitution identifies both a directly elected president and a prime minister responsible to the legislature. There are now some 58 countries in the world with a semi-presidential constitution. However, the academic wisdom is resolutely opposed to the adoption of semi-presidentialism and nascent democracies are advised to avoid this form of government. This paper examines the performance of semi-presidentialism. Particular attention is paid to ...

  7. Strategies of Financial Resources Attraction by Nascent Entrepreneurs in Russia compared with World-Wide Tendencies

    OpenAIRE

    Ekaterina Murzacheva

    2009-01-01

    The following research identifies factors that affect the financial decisions of nascent entrepreneurs starting a business in Russia compared to some other countries based on empirical data of Global Entrepreneurship Monitor. The main objective is to spotlight the role of the business climate, in particular the magnitude of the entrepreneur’s financial preferences.The study identifies preconditions for raising funds to set up a new business in terms of the connection between the entrepreneur’...

  8. Design Time Optimization for Hardware Watermarking Protection of HDL Designs

    Directory of Open Access Journals (Sweden)

    E. Castillo

    2015-01-01

    Full Text Available HDL-level design offers important advantages for the application of watermarking to IP cores, but its complexity also requires tools automating these watermarking algorithms. A new tool for signature distribution through combinational logic is proposed in this work. IPP@HDL, a previously proposed high-level watermarking technique, has been employed for evaluating the tool. IPP@HDL relies on spreading the bits of a digital signature at the HDL design level using combinational logic included within the original system. The development of this new tool for the signature distribution has not only extended and eased the applicability of this IPP technique, but it has also improved the signature hosting process itself. Three algorithms were studied in order to develop this automated tool. The selection of a cost function determines the best hosting solutions in terms of area and performance penalties on the IP core to protect. An 1D-DWT core and MD5 and SHA1 digital signatures were used in order to illustrate the benefits of the new tool and its optimization related to the extraction logic resources. Among the proposed algorithms, the alternative based on simulated annealing reduces the additional resources while maintaining an acceptable computation time and also saving designer effort and time.

  9. Inflammation reduces HDL protection against primary cardiac risk

    NARCIS (Netherlands)

    Corsetti, James P.; Gansevoort, Ron T.; Sparks, Charles E.; Dullaart, Robin P. F.

    2010-01-01

    P>Background We recently reported high high-density lipoprotein (HDL) cholesterol as a predictor of recurrent risk in a subgroup of postinfarction patients defined by hypercholesterolemia and high C-reactive protein (CRP) levels. We investigated whether a similar high-risk subgroup might exist for i

  10. Plasma HDL cholesterol and risk of myocardial infarction

    DEFF Research Database (Denmark)

    Voight, Benjamin F; Peloso, Gina M; Orho-Melander, Marju

    2012-01-01

    High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes...

  11. Plasma lipidomics discloses metabolic syndrome with a specific HDL phenotype.

    Science.gov (United States)

    Jové, Mariona; Naudí, Alba; Portero-Otin, Manuel; Cabré, Rosanna; Rovira-Llopis, Susana; Bañuls, Celia; Rocha, Milagros; Hernández-Mijares, Antonio; Victor, Victor M; Pamplona, Reinald

    2014-12-01

    Lipidomics reveals a remarkable diversity of lipids in human plasma. In this study, we have performed an in-depth lipidomic analysis of human plasma from healthy individuals and subjects with metabolic syndrome (MetS) in order to determine the lipidomic profile that allows prognosis of a pathological subpopulation with altered high-density lipoprotein (HDL) metabolism. The MetS population was categorized as having pathological or nonpathological HDL. Anthropometric parameters, cardiovascular risk markers, and lipoprotein subclasses of HDL and low-density lipoproteins were also evaluated. Lipidomic analysis revealed 357 differential molecules that were clustered (k means) in the two groups. The molecules identified in the whole lipidome showed that MetS subjects presented lower levels of glycerolipids and higher levels of glycerophospholipids with respect to control subjects. In contrast, when only statistically differential lipids were taken into account, differences were found between the two groups in almost cases. Furthermore, levels of saturated fatty acids were higher in patients with pathological HDL levels than in controls, whereas levels of unsaturated fatty acids were lower. These results highlight the potential of lipidomics as a clinical tool for risk assessment and monitoring of disease.

  12. Design time optimization for hardware watermarking protection of HDL designs.

    Science.gov (United States)

    Castillo, E; Morales, D P; García, A; Parrilla, L; Todorovich, E; Meyer-Baese, U

    2015-01-01

    HDL-level design offers important advantages for the application of watermarking to IP cores, but its complexity also requires tools automating these watermarking algorithms. A new tool for signature distribution through combinational logic is proposed in this work. IPP@HDL, a previously proposed high-level watermarking technique, has been employed for evaluating the tool. IPP@HDL relies on spreading the bits of a digital signature at the HDL design level using combinational logic included within the original system. The development of this new tool for the signature distribution has not only extended and eased the applicability of this IPP technique, but it has also improved the signature hosting process itself. Three algorithms were studied in order to develop this automated tool. The selection of a cost function determines the best hosting solutions in terms of area and performance penalties on the IP core to protect. An 1D-DWT core and MD5 and SHA1 digital signatures were used in order to illustrate the benefits of the new tool and its optimization related to the extraction logic resources. Among the proposed algorithms, the alternative based on simulated annealing reduces the additional resources while maintaining an acceptable computation time and also saving designer effort and time.

  13. [The real measurement of non-HDL-cholesterol: Atherogenic cholesterol].

    Science.gov (United States)

    Millán, Jesús; Hernández-Mijares, Antonio; Ascaso, Juan F; Blasco, Mariano; Brea, Angel; Díaz, Ángel; González-Santos, Pedro; Mantilla, Teresa; Pedro-Botet, Juan; Pintó, Xavier

    Lowe density lipoproteins (LDL) are the causal agent of cardiovascular diseases. In practice, we identify LDL with cholesterol transported in LDL (cLDL). So, cLDL has become the major target for cardiovascular prevention. Howewer, we have progressive evidences about the role of triglycerides rich lipoproteins, particularly those very low density lipoprotein (VLDL) in promotion and progression of atherosclerosis, that leads cholesterol in VLDL and its remanents as a potential therapeutic target. This feature is particularly important and of a great magnitude, in patients with hypertiglyceridemia. We can to considere, that the non-HDL cholesterol -cLDL+cVLDL+c-remmants+Lp(a)- is the real measurement of atherogenic cholesterol. In addition, non-HDL-cholesterol do not show any variations between postprandial states. In fact, non-HDL-cholesterol should be an excellent marker of atherogenic cholesterol, and an major therapeutic target in patients with atherogenic dyslipidaemia. According with different clinical trials and with the epidemiological and mendelian studies, in patients with high cardiovascular risk, optimal level of cLDL will be under 70mg/dl, and under 100 ng/dl for non-HDL-cholesterol; and in high risk patients, 100mg/dl and 130mg/dl, respectively. Copyright © 2016. Publicado por Elsevier España, S.L.U.

  14. Inflammation reduces HDL protection against primary cardiac risk

    NARCIS (Netherlands)

    Corsetti, James P.; Gansevoort, Ron T.; Sparks, Charles E.; Dullaart, Robin P. F.

    P>Background We recently reported high high-density lipoprotein (HDL) cholesterol as a predictor of recurrent risk in a subgroup of postinfarction patients defined by hypercholesterolemia and high C-reactive protein (CRP) levels. We investigated whether a similar high-risk subgroup might exist for

  15. Relation of Oxidative Stress and Impaired Fibrinolysis with HDL Biogenesis in Indonesian Men with Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Ida Paulina Sormin

    2010-04-01

    Full Text Available BACKGROUND: Biogenesis of HDL involves factors that regulate the synthesis, intravascular remodeling, and catabolism of HDL. Disturbance of these factors can lead to low concentration of HDL-C. Metabolic syndrome (MetS is characterized by low concentration of high-density lipoprotein cholesterol (HDL-C. In MetS occur several pathological conditions including oxidative stress and impaired fibrinolysis, which contribute to the risk of atherosclerosis process. The correlation between oxidative stress and impaired fibrinolysis with HDL biogenesis dysfunction and its correlation with low concentration of HDL-C has not been well understood and therefore needs to be further investigated. METHODS: This study was an observational study with crosssectional design, involving 163 adult men, aged 25-60 years with metabolic syndrome. Concentration of apoA-1, prebeta-1 HDL, CETP, F2-isoprostan, PAI-1, and HDL-C were measured. The apo A1/HDL ratio indicated HDL maturation, whereas the CETP/HDL-C and CETP/TG ratios indicated HDL catabolism. RESULTS: The study showed that there were a positive correlation between PAI-1 with apoA1/HDL-C ratios (r=0.226, p=0.005 and a negative correlation with the CETP/TG ratios (r=-0.215, p=0.007, whereas F2-isoprostan did not have correlation with HDL biogenesis factors. CONCLUSIONS: We concluded that there was correlation between impaired fibrinolysis with decreased HDL maturation and there was increased HDL catabolism leading to low HDL-C concentration in men with metabolic syndrome. KEYWORDS: F2-isoprostan, PAI-1, apoA-1, prebeta-1 HDL, CETP, metabolic syndrome.

  16. Capturing the dynamic nascent transcriptome during acute cellular responses: The serum response

    Directory of Open Access Journals (Sweden)

    Killeen S. Kirkconnell

    2016-06-01

    Full Text Available Dynamic regulation of gene expression via signal transduction pathways is of fundamental importance during many biological processes such as cell state transitioning, cell cycle progression and stress responses. In this study we used serum stimulation as a cell response paradigm to apply the nascent RNA Bru-seq technique in order to capture early dynamic changes in the nascent transcriptome. Our data provides an unprecedented view of the dynamics of genome-wide transcription during the first two hours of serum stimulation in human fibroblasts. While some genes showed sustained induction or repression, other genes showed transient or delayed responses. Surprisingly, the dynamic patterns of induction and suppression of response genes showed a high degree of similarity, suggesting that these opposite outcomes are triggered by a common set of signals. As expected, early response genes such as those encoding components of the AP-1 transcription factor and those involved in the circadian clock were immediately but transiently induced. Surprisingly, transcription of important DNA damage response genes and histone genes were rapidly repressed. We also show that RNA polymerase II accelerates as it transcribes large genes and this was independent of whether the gene was induced or not. These results provide a unique genome-wide depiction of dynamic patterns of transcription of serum response genes and demonstrate the utility of Bru-seq to comprehensively capture rapid and dynamic changes of the nascent transcriptome.

  17. Elastic coupling of nascent apCAM adhesions to flowing actin networks.

    Directory of Open Access Journals (Sweden)

    Cecile O Mejean

    Full Text Available Adhesions are multi-molecular complexes that transmit forces generated by a cell's acto-myosin networks to external substrates. While the physical properties of some of the individual components of adhesions have been carefully characterized, the mechanics of the coupling between the cytoskeleton and the adhesion site as a whole are just beginning to be revealed. We characterized the mechanics of nascent adhesions mediated by the immunoglobulin-family cell adhesion molecule apCAM, which is known to interact with actin filaments. Using simultaneous visualization of actin flow and quantification of forces transmitted to apCAM-coated beads restrained with an optical trap, we found that adhesions are dynamic structures capable of transmitting a wide range of forces. For forces in the picoNewton scale, the nascent adhesions' mechanical properties are dominated by an elastic structure which can be reversibly deformed by up to 1 µm. Large reversible deformations rule out an interface between substrate and cytoskeleton that is dominated by a number of stiff molecular springs in parallel, and favor a compliant cross-linked network. Such a compliant structure may increase the lifetime of a nascent adhesion, facilitating signaling and reinforcement.

  18. Non-HDL cholesterol goal attainment and its relationship with triglyceride concentrations among diabetic subjects with cardiovascular disease: A nationwide survey of 2674 individuals in Hungary.

    Science.gov (United States)

    Mark, Laszlo; Vallejo-Vaz, Antonio J; Reiber, Istvan; Paragh, György; Kondapally Seshasai, Sreenivasa Rao; Ray, Kausik K

    2015-07-01

    Non-HDL cholesterol represents the pro-atherogenic, apo-B-containing lipoprotein fraction of circulating lipids, and represents a secondary target for CVD prevention in people with diabetes. We therefore assessed the proportion of individuals with diabetes and CVD who attain a non-HDL-C goal of HDL-C and triglyceride-rich lipoproteins (TRL). Of 2674 diabetic subjects with baseline CVD in the Hungarian MULTI-GAP programme (mean age 64.8 years, mean HbA1c 7.2%), an LDL-C goal HDL-C goal HDL-C goal attainment declined at higher triglyceride concentrations; and graphically this relationship appeared to be continuously and inversely associated with triglyceride concentrations. In contrast, the relationship between LDL-C goal attainment was inversely and continuously associated with triglyceride levels up to about 2.5 mmol/L, after which the graphical appearance plateaued such that no further difference in LDL-C were observed beyond triglyceride levels of 2.5 mmol/L. With increasing triglyceride concentrations, non-HDL-C increased continuously, HDL-C decreased initially but later plateaued (at 1.5-2.0 [men] or 2.0-2.5 mmol/L [women]), LDL-C levels plateaued at about 2.0-2.5 mmol/L, and TRL-cholesterol (non-HDL-C minus LDL-C) rose continuously. In multivariable-adjusted models, elevated triglyceride concentrations, non-specialist care and uncontrolled blood pressure were inversely associated with non-HDL-C goal attainment. Triglyceride levels were more strongly associated with non-HDL-C than with LDL-C goal attainment (ORs per 1-SD increase in log-triglycerides was 0.74, 95% CI 0.61-0.89, for LDL-C goal attainment, and 0.49, 95% CI 0.38-0.61, for non-HDL-C goal attainment). Non-HDL-C goal attainment was suboptimal in people with diabetes and co-existing CVD. This was most marked at higher triglyceride levels, possibly due to higher levels of TRL. Crown Copyright © 2015. Published by Elsevier Ireland Ltd. All rights reserved.

  19. Implication of low HDL-c levels in patients with average LDL-c levels: a focus on oxidized LDL, large HDL subpopulation, and adiponectin.

    Science.gov (United States)

    Mascarenhas-Melo, Filipa; Sereno, José; Teixeira-Lemos, Edite; Marado, Daniela; Palavra, Filipe; Pinto, Rui; Rocha-Pereira, Petronila; Teixeira, Frederico; Reis, Flávio

    2013-01-01

    To evaluate the impact of low levels of high density lipoprotein cholesterol (HDL-c) on patients with LDL-c average levels, focusing on oxidative, lipidic, and inflammatory profiles. Patients with cardiovascular risk factors (n = 169) and control subjects (n = 73) were divided into 2 subgroups, one of normal HDL-c and the other of low HDL-c levels. The following data was analyzed: BP, BMI, waist circumference and serum glucose Total-c, TGs, LDL-c, oxidized LDL, total HDL-c and subpopulations (small, intermediate, and large), paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. In the control subgroup with low HDL-c levels, significantly higher values of BP and TGs and lower values of PON1 activity and adiponectin were found, versus control normal HDL-c subgroup. However, differences in patients' subgroups were clearly more pronounced. Indeed, low HDL-c subgroup presented increased HbA1c, TGs, non-HDL-c, Ox-LDL, hsCRP, VEGF, and small HDL-c and reduced adiponectin and large HDL. In addition, Ox-LDL, large-HDL-c, and adiponectin presented interesting correlations with classical and nonclassical markers, mainly in the normal HDL-c patients' subgroup. In conclusion, despite LDL-c average levels, low HDL-c concentrations seem to be associated with a poor cardiometabolic profile in a population with cardiovascular risk factors, which is better evidenced by traditional and nontraditional CV biomarkers, including Ox-LDL, large HDL-c, and adiponectin.

  20. Association of total cholesterol and HDL-C levels and outcome in coronary heart disease patients with heart failure

    Science.gov (United States)

    Zhao, Qin; Li, Jianfei; Yang, Jin; Li, Rongshan

    2017-01-01

    Abstract The aim of the study was to evaluate associations of total cholesterol (TC) and high density lipoprotein cholesterol (HDL-C) levels with prognosis in coronary heart disease (CHD) patients with heart failure (HF). Patients who were angiographical-diagnosis of CHD and echocardiographical-diagnosis of left ventricular ejection fraction (LVEF) Hs-CRP) was observed. TC was positively correlated with BMI and albumin, and HDL-C was inversely correlated with Hs-CRP. The associations of TC level and rehospitalization for HF and all-cause mortality were attenuated but consistently significant through model 1 to 4, with odds ratio (OR) of 0.97 (95% confidence interval [CI]: 0.92–0.99). Associations of HDL-C level and rehospitalization for HF and all-cause mortality were also consistently significant through model 1 to 4, with OR of 0.95 (95% CI: 0.90–0.98). Strength of association was attenuated prominently in model 3 after adjusted for Hs-CRP, and no change was observed after further adjusted for BMI and albumin. Higher baseline TC and HDL-C levels are associated with better outcome in CHD patients with HF. PMID:28248864

  1. A NEW CLASS OF NASCENT ECLIPSING BINARIES WITH EXTREME MASS RATIOS

    Energy Technology Data Exchange (ETDEWEB)

    Moe, Maxwell; Stefano, Rosanne Di, E-mail: mmoe@cfa.harvard.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, MS-10, Cambridge, MA 02138 (United States)

    2015-03-10

    Early B-type main-sequence (MS) stars (M {sub 1} ≈ 5-16 M {sub ☉}) with closely orbiting low-mass stellar companions (q = M {sub 2}/M {sub 1} < 0.25) can evolve to produce Type Ia supernovae, low-mass X-ray binaries, and millisecond pulsars. However, the formation mechanism and intrinsic frequency of such close extreme mass-ratio binaries have been debated, especially considering none have hitherto been detected. Utilizing observations of the Large Magellanic Cloud galaxy conducted by the Optical Gravitational Lensing Experiment, we have discovered a new class of eclipsing binaries in which a luminous B-type MS star irradiates a closely orbiting low-mass pre-MS companion that has not yet fully formed. The primordial pre-MS companions have large radii and discernibly reflect much of the light they intercept from the B-type MS primaries (ΔI {sub refl} ≈ 0.02-0.14 mag). For the 18 definitive MS + pre-MS eclipsing binaries in our sample with good model fits to the observed light-curves, we measure short orbital periods P = 3.0-8.5 days, young ages τ ≈ 0.6-8 Myr, and small secondary masses M {sub 2} ≈ 0.8-2.4 M {sub ☉} (q ≈ 0.07-0.36). The majority of these nascent eclipsing binaries are still associated with stellar nurseries, e.g., the system with the deepest eclipse ΔI {sub 1} = 2.8 mag and youngest age τ = 0.6 ± 0.4 Myr is embedded in the bright H II region 30 Doradus. After correcting for selection effects, we find that (2.0 ± 0.6)% of B-type MS stars have companions with short orbital periods P = 3.0-8.5 days and extreme mass ratios q ≈ 0.06-0.25. This is ≈10 times greater than that observed for solar-type MS primaries. We discuss how these new eclipsing binaries provide invaluable insights, diagnostics, and challenges for the formation and evolution of stars, binaries, and H II regions.

  2. The Inverse Relation of HDL Anti-Oxidative Functionality with Serum Amyloid a is Lost in Metabolic Syndrome Subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; de Boer, Jan Freark; Annema, Wijtske; Tietge, Uwe J. F.

    2013-01-01

    Objective: Anti-oxidative properties of high density lipoproteins (HDL) are relevant for atheroprotection. HDL carry serum amyloid A (SAA), which may impair HDL functionality. We questioned whether HDL anti-oxidative capacity is determined by SAA. Design and Methods: Relationships of HDL anti-oxidat

  3. The Inverse Relation of HDL Anti-Oxidative Functionality with Serum Amyloid a is Lost in Metabolic Syndrome Subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; de Boer, Jan Freark; Annema, Wijtske; Tietge, Uwe J. F.

    Objective: Anti-oxidative properties of high density lipoproteins (HDL) are relevant for atheroprotection. HDL carry serum amyloid A (SAA), which may impair HDL functionality. We questioned whether HDL anti-oxidative capacity is determined by SAA. Design and Methods: Relationships of HDL

  4. Major changes in the sphingophospholipidome of HDL in non-diabetic patients with metabolic syndrome.

    Science.gov (United States)

    Denimal, Damien; Nguyen, Amandine; Pais de Barros, Jean-Paul; Bouillet, Benjamin; Petit, Jean-Michel; Vergès, Bruno; Duvillard, Laurence

    2016-03-01

    Phospholipids and sphingolipids play a critical role in the protective effects of HDL against atherosclerosis. These properties are impaired in patients with metabolic syndrome, before the development of diabetes. We thus investigated whether HDL from patients with metabolic syndrome but normal fasting glycaemia present abnormalities in their sphingophospholipid profile. Using liquid chromatography/tandem mass spectrometry, we quantified the different species of the main phospholipids and sphingolipids in the HDL2 and HDL3 from 26 obese patients with metabolic syndrome but normal fasting glycaemia and 50 controls. Phosphatidylcholines, when expressed as the relative amount compared with total phospholipids and sphingolipids, were similar in both HDL2 and HDL3 in the two groups. Lysophosphatidylcholines were 41% (p = 0.0002) and 86% (p HDL2 and HDL3, respectively, from patients with metabolic syndrome than in those from controls. Phosphatidylinositols were also higher in HDL2 and HDL3 (respectively, +60 and + 103% (p HDL2 and HDL3 from patients with metabolic syndrome showed lower proportions of phosphatidylethanolamine-based plasmalogens (respectively -78 and -73%, p HDL from normoglycaemic obese patients with metabolic syndrome is profoundly modified, before the dysregulation of glycaemia. Most of the changes observed have pejorative effect in terms of vascular protection. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. High Speed Fault Injection Tool Implemented With Verilog HDL on FPGA for Testing Fault Tolerance Designs

    Directory of Open Access Journals (Sweden)

    G. Gopinath Reddy

    2013-11-01

    Full Text Available This paper presents an FPGA-based fault injection tool, called FITO that supports several synthesizable fault models for dependability analysis of digital systems modeled by Verilog HDL. Using the FITO, experiments can be performed in real-time with good controllability and observability. As a case study, an Open RISC 1200 microprocessor was evaluated using an FPGA circuit. About 4000 permanent, transient, and SEUfaults were injected into this microprocessor. The results show that the FITO tool is more than 79 times faster than a pure simulation-based fault injection with only 2.5% FPGA area overhead.

  6. Molecular dynamics simulation of human serum paraoxonase 1 in DPPC bilayer reveals a critical role of transmembrane helix H1 for HDL association.

    Science.gov (United States)

    Patra, Mahesh Chandra; Rath, Surya Narayan; Pradhan, Sukanta Kumar; Maharana, Jitendra; De, Sachinandan

    2014-01-01

    Serum paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-bound mammalian enzyme exhibiting antiatherosclerotic activity. Despite years of research, an accurate model for the binding interaction between PON1 and HDL has not been established. However, it is reported that anchoring of PON1 to HDL is mainly governed by an N-terminal alpha helix H1 and another short helix H2. Here, we studied the molecular association of full-length human PON1 (huPON1) with a HDL-mimetic dipalmitoylphosphatidylcholine (DPPC) bilayer using homology modeling and molecular dynamics simulations. Our results indicate that H1 is the highly dynamic part of huPON1, showing clockwise rotation of up to 30° within the DPPC bilayer. However, without phospholipid molecules, H1 experiences helical distortions, illustrating an incompatible HDL-anchoring conformation. Snorkeling interactions of K3, R18, and R27 together with aromatic locks formed by Y187, Y190, W194, and W202 are highly essential for anchoring of huPON1 to HDL's surface. Molecular mechanics/Poisson-Boltzmann solvent-accessible surface area (MM/PBSA) binding free energy calculation revealed that H1 displays greater binding affinity towards lipid molecules compared with H2 and H3, suggesting that H1 is the most probable HDL-binding domain of PON1. Binding free energy decomposition showed that K3, R18, and R27 interact with polar headgroups of DPPC membrane through electrostatic interaction. Moreover, Y187, Y190, W194, and W202 interact with DPPC lipids mainly through van der Waals interaction. Taken together, these results show that the transmembrane helix H1 along with the interfacial positively charged and aromatic resides were crucial for PON1's association with HDL particle. The current study will be useful towards understanding the antiatherosclerotic and bioscavenging properties of this promiscuous enzyme.

  7. 冠心病患者血清TG/HDL-C与LDL-C/HDL-C比值的比较分析

    Institute of Scientific and Technical Information of China (English)

    马业明

    2009-01-01

    目的:测定血清低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和胆固醇(TC)、三酰甘油(TG)等血脂括标,比较TG/HDL-C、LDL-C/HDL-C比值的水平,为冠心病患者的预测提供临床分析.方法:空腹抽取140例冠心病患者和130例健康体检者的静脉血,测定TC、TG、LDL-C、HDL-C,并计算TG/HDL-C、LDL-C/HDL-C的比值.结果:冠心病患者组TG/HDL-C、LDL-C/HDL-C比值分别为(2.24±0A2)、(1.47±0.49),比正常对照组显著增高(P<0.01),其中.LDL-C/HDL-C比值较TG/HDL-C比值差异更显著.结论:冠心患者血清TG、LDL-C显著增加,HDL-C水平显著下降.联合应用TG/HDL-C、LDL-C/HDL-C比值作为CHD的预测指标,较客观地反映出冠心病的非均-性改变,能及时发现CHD高危患者,进行早期合理干预,对防止动脉粥样硬化和冠心病的发生、发展有一定的临床意义.

  8. HDL surface lipids mediate CETP binding as revealed by electron microscopy and molecular dynamics simulation

    Science.gov (United States)

    Zhang, Meng; Charles, River; Tong, Huimin; Zhang, Lei; Patel, Mili; Wang, Francis; Rames, Matthew J.; Ren, Amy; Rye, Kerry-Anne; Qiu, Xiayang; Johns, Douglas G.; Charles, M. Arthur; Ren, Gang

    2015-03-01

    Cholesteryl ester transfer protein (CETP) mediates the transfer of cholesterol esters (CE) from atheroprotective high-density lipoproteins (HDL) to atherogenic low-density lipoproteins (LDL). CETP inhibition has been regarded as a promising strategy for increasing HDL levels and subsequently reducing the risk of cardiovascular diseases (CVD). Although the crystal structure of CETP is known, little is known regarding how CETP binds to HDL. Here, we investigated how various HDL-like particles interact with CETP by electron microscopy and molecular dynamics simulations. Results showed that CETP binds to HDL via hydrophobic interactions rather than protein-protein interactions. The HDL surface lipid curvature generates a hydrophobic environment, leading to CETP hydrophobic distal end interaction. This interaction is independent of other HDL components, such as apolipoproteins, cholesteryl esters and triglycerides. Thus, disrupting these hydrophobic interactions could be a new therapeutic strategy for attenuating the interaction of CETP with HDL.

  9. Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; de Boer, Jan Freark; Perton, Frank G.; Annema, Wijtske; de Vries, Rindert; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    2012-01-01

    Background Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes mellit

  10. Increased LCAT activity and hyperglycaemia decrease the antioxidative functionality of HDL

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; de Boer, Jan Freark; Perton, Frank G.; Annema, Wijtske; de Vries, Rindert; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    Background Type 2 diabetes mellitus increases the risk of atherosclerotic cardiovascular disease. Antioxidative properties of high density lipoprotein (HDL) are important for atheroprotection. This study investigated whether the antioxidative functionality of HDL is altered in type 2 diabetes

  11. Apolipoprotein M binds oxidized phospholipids and increases the antioxidant effect of HDL

    DEFF Research Database (Denmark)

    Elsøe, Sara; Ahnström, Josefin; Christoffersen, Christina;

    2012-01-01

    Oxidation of LDL plays a key role in the development of atherosclerosis. HDL may, in part, protect against atherosclerosis by inhibiting LDL oxidation. Overexpression of HDL-associated apolipoprotein M (apoM) protects mice against atherosclerosis through a not yet clarified mechanism. Being...... a lipocalin, apoM contains a binding pocket for small lipophilic molecules. Here, we report that apoM likely serves as an antioxidant in HDL by binding oxidized phospholipids, thus enhancing the antioxidant potential of HDL....

  12. HDL Implementation of Low Density Parity Check (LDPC Decoder

    Directory of Open Access Journals (Sweden)

    Pawandip Kaur

    2012-03-01

    Full Text Available Low-Density Parity-Check (LDPC codes are one of the most promising error-correcting codes approaching Shannon capacity and have been adopted in many applications. These codes offer huge advantages in terms of coding gain, throughput and power dissipation. Error correction algorithms are often implemented in hardware for fast processing to meet the real-time needs of communication systems. However hardwareimplementation of LDPC decoders using traditional Hardware Description Language (HDL based approach is a complex and time consuming task. In this paper HDL Implementation of Low Density Parity Check Decoder architecture is presented with different rates i.e. 1/2, 2/3, 3/4, 4/7, 8/9, 9/10 and variable data lengths i.e. 8, 16, 32, 64, 128, 256 bits and consequent changeable precision factor.

  13. HDL functionality in South Asians as compared to white Caucasians.

    Science.gov (United States)

    Bakker, L E H; Boon, M R; Annema, W; Dikkers, A; van Eyk, H J; Verhoeven, A; Mayboroda, O A; Jukema, J W; Havekes, L M; Meinders, A E; Willems van Dijk, K; Jazet, I M; Tietge, U J F; Rensen, P C N

    2016-08-01

    South Asians have an exceptionally high risk of developing cardiovascular disease compared to white Caucasians. A contributing factor might be dysfunction of high density lipoprotein (HDL). We aimed to compare HDL function in different age groups of both ethnicities. HDL functionality with respect to cholesterol efflux, anti-oxidation and anti-inflammation was determined using fasting, apoB-depleted, plasma samples from South Asian and white Caucasian neonates (n = 14 each), adolescent healthy men (n = 12 each, 18-25 y), and adult overweight men (n = 12 each, 40-50 y). Adolescents were subjected to a 5-day high fat high calorie diet (HCD) and adults to an 8-day very low calorie diet (LCD). Additionally, HDL composition was measured in adolescents and adults using (1)H-NMR spectroscopy. Anti-oxidative capacity was lower in South Asian adults before LCD (19.4 ± 2.1 vs. 25.8 ± 1.2%, p = 0.045, 95%-CI = [0.1; 12.7]) and after LCD (16.4 ± 2.4 vs. 27.6 ± 2.7%, p = 0.001, 95%-CI = [4.9; 17.5]). Anti-inflammatory capacity was reduced in South Asian neonates (23.8 ± 1.2 vs. 34.9 ± 1.3%, p = 0.000001, 95%-CI = [-14.6; -7.5]), and was negatively affected by an 8-day LCD only in South Asian adults (-12.2 ± 4.3%, p = 0.005, 95%-CI = [-5.9; -1.2]). Cholesterol efflux capacity was increased in response to HCD in adolescents (South Asians: +6.3 ± 2.9%, p = 0.073, 95%-CI = [-0.02; 0.46], Caucasians: +11.8 ± 3.4%, p = 0.002, 95%-CI = [0.17;0.65]) and decreased after LCD in adults (South Asians: -10.3 ± 2.4%, p HDL showed no differences between ethnicities, cholesterol efflux correlated best with cholesterol and phospholipid within small HDL compared to other HDL subclasses and constituents. Impaired HDL functionality in South Asians may be a contributing factor to their high CVD risk. NTR 2473 (URL: http://www.trialregister.nl/). Copyright © 2016 The Italian Society of Diabetology, the Italian Society for the Study of

  14. Association of Serum Triglyceride to HDL Cholesterol Ratio with All-Cause and Cardiovascular Mortality in Incident Hemodialysis Patients.

    Science.gov (United States)

    Chang, Tae Ik; Streja, Elani; Soohoo, Melissa; Kim, Tae Woo; Rhee, Connie M; Kovesdy, Csaba P; Kashyap, Moti L; Vaziri, Nosratola D; Kalantar-Zadeh, Kamyar; Moradi, Hamid

    2017-04-03

    Elevated serum triglyceride/HDL cholesterol (TG/HDL-C) ratio has been identified as a risk factor for cardiovascular (CV) disease and mortality in the general population. However, the association of this important clinical index with mortality has not been fully evaluated in patients with ESRD on maintenance hemodialysis (MHD). We hypothesized that the association of serum TG/HDL-C ratio with all-cause and CV mortality in patients with ESRD on MHD is different from the general population. We studied the association of serum TG/HDL-C ratio with all-cause and CV mortality in a nationally representative cohort of 50,673 patients on incident hemodialysis between January 1, 2007 and December 31, 2011. Association of baseline and time-varying TG/HDL-C ratios with mortality was assessed using Cox proportional hazard regression models, with adjustment for multiple variables, including statin therapy. During the median follow-up of 19 months (interquartile range, 11-32 months), 12,778 all-cause deaths and 4541 CV deaths occurred, respectively. We found that the 10th decile group (reference: sixth deciles of TG/HDL-C ratios) had significantly lower risk of all-cause mortality (hazard ratio, 0.91 [95% confidence interval, 0.83 to 0.99] in baseline and 0.86 [95% confidence interval, 0.79 to 0.94] in time-varying models) and CV mortality (hazard ratio, 0.83 [95% confidence interval, 0.72 to 0.96] in baseline and 0.77 [95% confidence interval, 0.66 to 0.90] in time-varying models). These associations remained consistent and significant across various subgroups. Contrary to the general population, elevated TG/HDL-C ratio was associated with better CV and overall survival in patients on hemodialysis. Our findings provide further support that the nature of CV disease and mortality in patients with ESRD is unique and distinct from other patient populations. Hence, it is vital that future studies focus on identifying risk factors unique to patients on MHD and decipher the underlying

  15. A complex phenotype in a child with familial HDL deficiency due to a novel frameshift mutation in APOA1 gene (apoA-IGuastalla).

    Science.gov (United States)

    Pisciotta, Livia; Vitali, Cecilia; Favari, Elda; Fossa, Paola; Adorni, Maria Pia; Leone, Daniela; Artom, Nathan; Fresa, Raffaele; Calabresi, Laura; Calandra, Sebastiano; Bertolini, Stefano

    2015-01-01

    We describe a kindred with high-density lipoprotein (HDL) deficiency due to APOA1 gene mutation in which comorbidities affected the phenotypic expression of the disorder. An overweight boy with hypertriglyceridemia (HTG) and HDL deficiency (HDL cholesterol 0.39 mmol/L, apoA-I 40 mg/dL) was investigated. We sequenced the candidate genes for HTG (LPL, APOC2, APOA5, GPIHBP1, LMF1) and HDL deficiency (LCAT, ABCA1 and APOA1), analyzed HDL subpopulations, measured cholesterol efflux capacity (CEC) of sera and constructed a model of the mutant apoA-I. No mutations in HTG-related genes, ABCA1 and LCAT were found. APOA1 sequence showed that the proband, his mother and maternal grandfather were heterozygous of a novel frameshift mutation (c.546_547delGC), which generated a truncated protein (p.[L159Afs*20]) containing 177 amino acids with an abnormal C-terminal tail of 19 amino acids. Trace amounts of this protein were detectable in plasma. Mutation carriers had reduced levels of LpA-I, preβ-HDL and large HDL and no detectable HDL-2 in their plasma; their sera had a reduced CEC specifically the ABCA1-mediated CEC. Metabolic syndrome in the proband explains the extremely low HDL cholesterol level (0.31 mmol/L), which was half of that found in the other carriers. The proband's mother and grandfather, both presenting low plasma low-density lipoprotein cholesterol, were carriers of the β-thalassemic trait, a condition known to be associated with a reduced low-density lipoprotein cholesterol and a reduced prevalence of cardiovascular disease. This trait might have delayed the development of atherosclerosis related to HDL deficiency. In these heterozygotes for apoA-I truncation, the metabolic syndrome has deleterious effect on HDL system, whereas β-thalassemia trait may delay the onset of cardiovascular disease. Copyright © 2015 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  16. Association of cholesterol, LDL, HDL, cholesterol/ HDL and triglyceride with all-cause mortality in life insurance applicants.

    Science.gov (United States)

    Fulks, Michael; Stout, Robert L; Dolan, Vera F

    2009-01-01

    Determine the relationship between various lipid tests and all-cause mortality in life insurance applicants stratified by age and sex. By use of the Social Security Death Master File, mortality was determined in 1,488,572 life insurance applicants from whom blood samples were submitted to Clinical Reference Laboratory. There were 41,020 deaths observed in this healthy adult population during a median follow-up of 12 years (range 10 to 14 years). Results were stratified by 4 age-sex subpopulations: females, ages 20 to 59 or 60+; and males, ages 20 to 59 or 60+. Those with serum albumin or = 2.1 mmol/L were excluded. The middle 50% of lipid values specific to each of these 4 age-sex subpopulations was used as the reference band. The mortality rates in bands representing other percentiles of lipid values were compared with the mortality rate in the reference band within each age-sex subpopulation. In contrast to some published findings from general populations, lipid test results are only moderately predictive of all-cause mortality risk in a life insurance applicant population and that risk is dependent on age and sex. At ages below 60, HDL values are associated with a "J" shaped mortality curve and at ages 60+, total cholesterol is associated with a "U" shaped curve. The total cholesterol/HDL ratio may serve as a useful single measure to predict mortality risk, but only if stratified by age and sex, and only if high HDL values at younger ages and lower total cholesterol values at ages 60+ are recognized as being associated with increased risk as well. Using LDL or non-HDL cholesterol instead of total cholesterol does not improve mortality risk discrimination; neither does using total cholesterol or triglyceride values in addition to the total cholesterol/HDL ratio. The total cholesterol/HDL ratio is the best single measure of all-cause mortality risk among the various lipid tests but is useful only if viewed on an age- and sex-specific basis and is only a modest

  17. Effects of HDL-modifiers on cardiovascular outcomes: a meta-analysis of randomized trials

    NARCIS (Netherlands)

    Verdoia, M.; Schaffer, A.; Suryapranata, H.; Luca, G. De

    2015-01-01

    BACKGROUND AND AIM: High density lipoproteins (HDL) have been addressed as a potential strategy for cardiovascular prevention, with great controversies on pharmacological approaches for HDL-elevation. Our aim was to compare HDL-rising treatment with niacin or CETP-inhibitors with optimal medical the

  18. Evaluation of The Predicative Value of LDL-C/HDL-C and TG/HDL-C Ratio for Coronary Heart Disease%LDL-C/HDL-C及TG/HDL-C比值对冠心病的预测价值的评价

    Institute of Scientific and Technical Information of China (English)

    刘梅颜; 郭丹杰; 胡大一; 徐成斌; 崔永东

    2002-01-01

    目的探讨LDL-C/HDL-C比值、TG/HDL-C比值与冠心病之间的相关性.方法分析104例经冠脉造影确诊的冠心病患者(CHD组)及92例冠脉造影阴性者(对照组)LDL-C/HDL-C比值及TG/HDL-C比值对冠心病的诊断价值.结果冠心病组患者LDL-C/HDL-C比值、TG/HDL-C比值水平及异常率均明显高于对照组,相关分析显示,LDL-C/HDL-C比值及TG/HDL-C比值与冠心病相关,前者与CHD回归关系更强,且两比值之间呈正相关.结论LDL-C/HDL-C及TG/HDL-C比值可作为预测CHD的指标.与TG/HDL-C相比,LDL-C/HDL-C比值水平与CHD相关更强.

  19. Clinical Analysis and Evaluation for The Predicative Value Of LDL-C/HDL-C and TG/HDL-C Ratio for Coronary Heart Disease%LDL-C/HDL-C和TG/HDL-C比值对冠心病预测评价的I临床研究

    Institute of Scientific and Technical Information of China (English)

    张风菊; 翟春玺

    2008-01-01

    目的 探讨LDL-C/HDL-C、TG/HDL-C比值与冠心病预后相关性.方法 收集68例经冠脉造影确诊的冠心病患者(CHD))及57例冠脉造影阴性者(对照组),冠造前空腹12小时后清晨采集血样上机测定血脂,并计算出LDL-C/HDL-C比值、TG/HDL-C比值.结果 CHD组患者LDL-C和TG与HDL-C比值水平及异常率均明显高于对照组,相关分析显示,LDL-C/HDL-C比值及TG/HDL-C比值与冠心病相关,LDL-C/HDL-C比值与冠心病回归关系更强,且两比值之间呈正相关.结论 LDL-C/HDL-C及TG/HDL-C比值可作为预测CHD的指标.与TG/HDL-C相比,LDL-c/HDL-C比值水平与冠心病相关更强.

  20. HDL measures, particle heterogeneity, proposed nomenclature, and relation to atherosclerotic cardiovascular events

    Science.gov (United States)

    A growing body of evidence from epidemiological data, animal studies, and clinical trials supports HDL as the next target to reduce residual cardiovascular risk in statin-treated, high-risk patients. For more than 3 decades, HDL cholesterol has been employed as the principal clinical measure of HDL ...

  1. Serum amyloid A enrichment impairs the anti-inflammatory ability of HDL from diabetic nephropathy patients.

    Science.gov (United States)

    Mao, Jing Yan; Sun, Jia Teng; Yang, Ke; Shen, Wei Feng; Lu, Lin; Zhang, Rui Yan; Tong, Xuemei; Liu, Yan

    2017-10-01

    Impaired anti-inflammatory ability of high-density lipoprotein (HDL) has been demonstrated in patients with type-2 diabetes mellitus (T2DM). However, whether HDL from patients with diabetic nephropathy (DN) suffers additional damage remains unknown. This study compared the anti-inflammatory capacities of HDL from healthy controls, T2DM patients with normal renal function, and T2DM patients with DN. HDL was isolated from healthy controls (n=33) and T2DM patients with normal renal function (n=21), chronic kidney disease (CKD) (n=27), and end-stage renal disease (ESRD) (n=27). Human peripheral blood mononuclear cells (PBMCs) from healthy volunteers were pretreated with HDL (100μg/mL) for 1h, then incubated with lipopolysaccharide (LPS) (50ng/mL) for 24h. The anti-inflammatory ability of HDL was measured as the secretion of TNF-α in LPS-activated monocytes. The anti-inflammatory ability of HDL was gradually impaired as kidney function declined. Serum amyloid A (SAA) concentration in HDL(DN) significantly increased and was positively correlated with the impaired anti-inflammatory ability of HDL (Pearson r=0.315, P=0.006). Furthermore, HDL supplemented with SAA significantly increased TNF-α release from PBMCs compared with that from control HDL. These findings identified an impaired anti-inflammatory capacity of HDL from DN patients, which might be attributable to SAA enrichment. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population

    DEFF Research Database (Denmark)

    Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Jensen, Gorm B;

    2004-01-01

    Homozygosity for mutations in ABC transporter A1 (ABCA1) causes Tangier disease, a rare HDL-deficiency syndrome. Whether heterozygosity for genetic variation in ABCA1 also contributes to HDL cholesterol (HDL-C) levels in the general population is presently unclear. We determined whether mutations...

  3. 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.

  4. Associations of anthropometry and lifestyle factors with HDL subspecies according to apolipoprotein C-III.

    Science.gov (United States)

    Koch, Manja; Furtado, Jeremy D; Jiang, Gordon Z; Gray, Brianna E; Cai, Tianxi; Sacks, Frank; Tjønneland, Anne; Overvad, Kim; Jensen, Majken K

    2017-06-01

    The presence of apoC-III on HDL impairs HDL's inverse association with coronary heart disease (CHD). Little is known about modifiable factors explaining variation in HDL subspecies defined according to apoC-III. The aim was to investigate cross-sectional associations of anthropometry and lifestyle with HDL subspecies in 3,631 participants from the Diet, Cancer, and Health study originally selected for a case-cohort study (36% women; age 50-65 years) who were all free of CHD. Greater adiposity and less activity were associated with higher HDL containing apoC-III and lower HDL lacking apoC-III. Per each 15 cm higher waist circumference, the level of HDL containing apoC-III was 2.8% higher (95% CI: 0.4, 5.3; P = 0.024) and the level of HDL not containing apoC-III was 4.7% lower (95% CI: -6.0, -3.4; P = HDL containing apoC-III and 0.5% higher (95% CI: 0.1, 1.0; P = 0.029) HDL lacking apoC-III. Lower alcohol consumption was associated with lower HDL lacking apoC-III (percent difference per 15 g/day: 1.58 (95% CI: 0.84, 2.32; P = HDL subspecies profile. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Effects of HDL-modifiers on cardiovascular outcomes: a meta-analysis of randomized trials

    NARCIS (Netherlands)

    Verdoia, M.; Schaffer, A.; Suryapranata, H.; Luca, G. De

    2015-01-01

    BACKGROUND AND AIM: High density lipoproteins (HDL) have been addressed as a potential strategy for cardiovascular prevention, with great controversies on pharmacological approaches for HDL-elevation. Our aim was to compare HDL-rising treatment with niacin or CETP-inhibitors with optimal medical

  6. Nascent histamine induces α-synuclein and caspase-3 on human cells

    Energy Technology Data Exchange (ETDEWEB)

    Caro-Astorga, Joaquín; Fajardo, Ignacio; Ruiz-Pérez, María Victoria; Sánchez-Jiménez, Francisca; Urdiales, José Luis, E-mail: jlurdial@uma.es

    2014-09-05

    Highlights: • Nascent histamine alters cyclin expression pattern. • Nascent histamine increases expression of α-synuclein. • Nascent histamine activates caspase-3. - Abstract: Histamine (Hia) is the most multifunctional biogenic amine. It is synthetized by histidine decarboxylase (HDC) in a reduced set of mammalian cell types. Mast cells and histaminergic neurons store Hia in specialized organelles until the amine is extruded by exocytosis; however, other immune and cancer cells are able to produce but not store Hia. The intracellular effects of Hia are still not well characterized, in spite of its physiopathological relevance. Multiple functional relationships exist among Hia metabolism/signaling elements and those of other biogenic amines, including growth-related polyamines. Previously, we obtained the first insights for an inhibitory effect of newly synthetized Hia on both growth-related polyamine biosynthesis and cell cycle progression of non-fully differentiated mammalian cells. In this work, we describe progress in this line. HEK293 cells were transfected to express active and inactive versions of GFP-human HDC fusion proteins and, after cell sorting by flow cytometry, the relative expression of a large number of proteins associated with cell signaling were measured using an antibody microarray. Experimental results were analyzed in terms of protein–protein and functional interaction networks. Expression of active HDC induced a cell cycle arrest through the alteration of the levels of several proteins such as cyclin D1, cdk6, cdk7 and cyclin A. Regulation of α-synuclein and caspase-3 was also observed. The analyses provide new clues on the molecular mechanisms underlying the regulatory effects of intracellular newly synthetized Hia on cell proliferation/survival, cell trafficking and protein turnover. This information is especially interesting for emergent and orphan immune and neuroinflammatory diseases.

  7. Do HDL and LDL subfractions play a role in atherosclerosis in end-stage renal disease (ESRD) patients?

    Science.gov (United States)

    Gluba-Brzózka, Anna; Franczyk, Beata; Banach, Maciej; Rysz-Górzyńska, Magdalena

    2017-01-01

    Significantly increased cardiovascular mortality in patients with chronic kidney (CKD) disease cannot be explained by traditional risk factors. Recent studies revealed that the quality of HDL and LDL cholesterol may be more important than their serum levels. The aim of this study was to assess which LDL and HDL subfractions were more abundant in end-stage renal disease (ESRD) patients and to analyse whether subfraction distribution could be associated with accelerated atherosclerotic processes. This study included 50 ESRD patients undergoing dialysis and 20 healthy volunteers. LDL and HDL subfractions were analysed in serum with the use of Lipoprint system. All patients had intima-media thickness (IMT) measured. Statistically significant differences in subfractions between control and study group were observed in case of: HDL1 (p HDL2 (p = 0.009), HDL3 (p HDL4 (p = 0.003), HDL5 (p = 0.01), HDL7 (p HDL8 (p HDL9 (p HDL10 (p HDL (p HDL Small (p HDL and LDL subfraction distribution between haemodialysis patients with normal and increased IMT: HDL6 (p = 0.020), HDL Large (HDL1-3) (p = 0.017), HDL Intermediate (HDL4-7) (p = 0.017). This study revealed that ESRD influenced HDL subfractions. In HD patients, large HDL subfractions are more abundant while small HDL fraction is more frequent in healthy persons. It failed to show the influence of end-stage disease on LDL subfraction levels. Shift in HDL subfractions might be responsible for the increased risk of atherosclerosis in CKD patients.

  8. Endothelial dysfunction correlates with plasma fibrinogen and HDL cholesterol in type 2 diabetic patients with coronary artery disease.

    Science.gov (United States)

    Bosevski, M; Borozanov, V; Peovska, I; Georgievska-Ismail, L

    2007-01-01

    Assessment of endothelial dysfunction (ED) in type 2 diabetic patients with coronary artery disease (CAD) and estimation of correlation of ED with metabolic parameters: low HDL, hypertriglyceridemia, obesity, systolic blood pressure and with inflammatory-hemostatic parameters: CRP and fibrinogen. 42 patients (age 60.0 +/- 8.5 years) with diagnosed type 2 diabetes and CAD were randomly included in a cross sectional study. B-mode ultrasound system with a linear transducer 7.5 MHz was used for evaluation of flow mediated vasodilation in brachial artery (FMV). FMV was presented as the percentage increase in brachial artery diameter, within 30 s after limb ischemia, previously provoked by cuff inflation. Percentage value up to 10% was defined as ED. Bivariate linear correlation model presented significant correlation between plasma fibrinogen and FMV percentage, with r -0.47, p HDL HDL (OR 5.16, 95% CI 0.53-60.39) as factors correlated with the presence of endothelial dysfunction. These results presented plasma fibrinogen level and low HDL diabetic patients with coronary artery disease (Tab. 8, Fig. 1, Ref. 25). Full Text (Free, PDF) www.bmj.sk.

  9. High Pre-β1 HDL Concentrations and Low Lecithin: Cholesterol Acyltransferase Activities Are Strong Positive Risk Markers for Ischemic Heart Disease and Independent of HDL-Cholesterol

    Science.gov (United States)

    Sethi, Amar A.; Sampson, Maureen; Warnick, Russell; Muniz, Nehemias; Vaisman, Boris; Nordestgaard, Børge G.; Tybjærg-Hansen, Anne; Remaley, Alan T.

    2016-01-01

    BACKGROUND We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors. METHODS Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women ≥735 mg/L; men ≥619 mg/L) or low HDL-C (n = 42; women ≤387 mg/L; men ≤341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay. RESULTS Pre-β1 HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) μmol · L−1 · h−1; P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) μmol · L−1 · h−1; P = 0.03] HDL-C groups. ROC curves for pre-β1 HDL in the high–HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61–0.81) for predicting IHD, which increased to 0.92 (0.87–0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-β1 HDL was observed (r2 = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r2 = 0.56; P < 0.0001). CONCLUSIONS IHD was associated with high pre-β1 HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-β1 HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease. PMID:20511449

  10. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Otvos, James D.; James, Richard W.

    2014-01-01

    Objectives: We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2 diabe

  11. Serum paraoxonase-1 activity is more closely related to HDL particle concentration and large HDL particles than to HDL cholesterol in Type 2 diabetic and non-diabetic subjects

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Otvos, James D.; James, Richard W.

    Objectives: We determined relationships of the anti-oxidative enzyme, paraoxonase-1 (PON-1), with high density lipoprotein (HDL) subfractions, and tested whether these relationships are stronger than those with HDL cholesterol and apolipoprotein A-I (apoA-I) in subjects with and without type 2

  12. Regional variations in HDL metabolism in human fat cells: effect of cell size

    Energy Technology Data Exchange (ETDEWEB)

    Despres, J.; Fong, B.S.; Julien, P.; Jimenez, J.; Angel, A.

    1987-05-01

    Abdominal obesity is related to reduced plasma high-density lipoprotein (HDL) cholesterol, and both are associated with cardiovascular disease risk. The authors have observed that plasma membranes from abdominal subcutaneous adipocytes have a greater HDL binding capacity than omental fat cell plasma membranes. The present study examined whether these binding characteristics could be due to differences in fat cell size or cholesterol concentration between the two adipose depots. Abdominal subcutaneous and deep omental fat were obtained from massively obese patients at surgery. Subcutaneous abdominal fat cells were significantly larger and their cellular cholesterol content greater than omental adipocytes. The uptake of HDL by collagenase-isolated fat cells was studied by incubating the cells for 2 h at 37/sup 0/C with 10 ..mu..g/ml /sup 125/I-HDL/sub 2/ or /sup 125/I-HDL/sub 3/. In both depots, the cellular uptake of /sup 125/I-HDL/sub 2/ and /sup 125/I-HDL/sub 3/ was specifically inhibited by addition of 25-fold excess unlabeled HDL and a close correlation was observed between the cellular uptake of /sup 125/I-HDL/sub 2/ and /sup 125/I-HDL/sub 3/. In obese patients, the uptake of /sup 125/I-HDL was higher in subcutaneous cells than in omental cells. The cellular /sup 125/I-HDL uptake was significantly correlated with adipocyte size and fat cell cholesterol content but not with adipocyte cholesterol concentration. These results suggest that the higher HDL uptake observed in subcutaneous cells compared with omental cells in obesity is the result of differences in adipocyte size rather than differences in the cholesterol concentration (cholesterol-to-triglyceride ratio). The increased interaction of HDL with hypertrophied abdominal adipocytes may play an important role in determining the lipid composition of HDL in obesity.

  13. TRAK2, a novel regulator of ABCA1 expression, cholesterol efflux and HDL biogenesis.

    Science.gov (United States)

    Lake, Nicole J; Taylor, Rachael L; Trahair, Hugh; Harikrishnan, K N; Curran, Joanne E; Almeida, Marcio; Kulkarni, Hemant; Mukhamedova, Nigora; Hoang, Anh; Low, Hann; Murphy, Andrew J; Johnson, Matthew P; Dyer, Thomas D; Mahaney, Michael C; Göring, Harald H H; Moses, Eric K; Sviridov, Dmitri; Blangero, John; Jowett, Jeremy B M; Bozaoglu, Kiymet

    2017-06-26

    The recent failures of HDL-raising therapies have underscored our incomplete understanding of HDL biology. Therefore there is an urgent need to comprehensively investigate HDL metabolism to enable the development of effective HDL-centric therapies. To identify novel regulators of HDL metabolism, we performed a joint analysis of human genetic, transcriptomic, and plasma HDL-cholesterol (HDL-C) concentration data and identified a novel association between trafficking protein, kinesin binding 2 (TRAK2) and HDL-C concentration. Here we characterize the molecular basis of the novel association between TRAK2 and HDL-cholesterol concentration. Analysis of lymphocyte transcriptomic data together with plasma HDL from the San Antonio Family Heart Study (n = 1240) revealed a significant negative correlation between TRAK2 mRNA levels and HDL-C concentration, HDL particle diameter and HDL subspecies heterogeneity. TRAK2 siRNA-mediated knockdown significantly increased cholesterol efflux to apolipoprotein A-I and isolated HDL from human macrophage (THP-1) and liver (HepG2) cells by increasing the mRNA and protein expression of the cholesterol transporter ATP-binding cassette, sub-family A member 1 (ABCA1). The effect of TRAK2 knockdown on cholesterol efflux was abolished in the absence of ABCA1, indicating that TRAK2 functions in an ABCA1-dependent efflux pathway. TRAK2 knockdown significantly increased liver X receptor (LXR) binding at the ABCA1 promoter, establishing TRAK2 as a regulator of LXR-mediated transcription of ABCA1. We show, for the first time, that TRAK2 is a novel regulator of LXR-mediated ABCA1 expression, cholesterol efflux, and HDL biogenesis. TRAK2 may therefore be an important target in the development of anti-atherosclerotic therapies.

  14. Lipid-free Apolipoprotein A-I Structure: Insights into HDL Formation and Atherosclerosis Development

    Science.gov (United States)

    Mei, Xiaohu; Atkinson, David

    2015-01-01

    Apolipoprotein A-I is the major protein in high-density lipoprotein (HDL) and plays an important role during the process of reverse cholesterol transport (RCT). Knowledge of the high-resolution structure of full-length apoA-I is vital for a molecular understanding of the function of HDL at the various steps of the RCT pathway. Due to the flexible nature of apoA-I and aggregation properties, the structure of full-length lipid-free apoA-I has evaded description for over three decades. Sequence analysis of apoA-I suggested that the amphipathic α-helix is the structural motif of exchangeable apolipoprotein, and NMR, X-ray and MD simulation studies have confirmed this. Different laboratories have used different methods to probe the secondary structure distribution and organization of both the lipid-free and lipid-bound apoA-I structure. Mutation analysis, synthetic peptide models, surface chemistry and crystal structures have converged on the lipid-free apoA-I domain structure and function: the N-terminal domain [1–184] forms a helix bundle while the C-terminal domain [185–243] mostly lacks defined structure and is responsible for initiating lipid-binding, aggregation and is also involved in cholesterol efflux. The first 43 residues of apoA-I are essential to stabilize the lipid-free structure. In addition, the crystal structure of C-terminally truncated apoA-I suggests a monomer-dimer conversation mechanism mediated through helix 5 reorganization and dimerization during the formation of HDL. Based on previous research, we have proposed a structural model for full-length monomeric apoA-I in solution and updated the HDL formation mechanism through three intermediate states. Mapping the known natural mutations on the full-length monomeric apoA-I model provides insight into atherosclerosis development through disruption of the N-terminal helix bundle or deletion of the C-terminal lipid-binding domain. PMID:26048453

  15. HDL subfractions analysis: a new laboratory diagnostic assay for patients with cardiovascular diseases and dyslipoproteinemia.

    Science.gov (United States)

    Oravec, Stanislav; Dostal, Elisabeth; Dukát, Andrej; Gavorník, Peter; Kucera, Marek; Gruber, Kristína

    2011-01-01

    The HDL family forms a protective part of plasma lipoproteins. It consists of large HDL, intermediate HDL, and small HDL subclasses. The large HDL and intermediate HDL subclasses are considered anti-atherogenic parts of the HDL family. The atherogenicity of the small HDL subclass is currently the subject of much discussion. In the patient group with the diagnosis of cardiovascular disease (arterial hypertension, coronary heart disease) and in individuals with a non-atherogenic hypercholesterolemia, a type of lipoprotein profile (either a non-atherogenic phenotype A, or an atherogenic phenotype B) was identified, and a concentration of small dense LDL (sdLDL) was analyzed. The aim of this study was to identify the major representative of the HDL subclasses in the individuals with cardiovascular diseases, who had an atherogenic lipoprotein phenotype B, and in the individuals with the diagnosis of non-atherogenic hyper-betalipoproteinemia LDL1,2, who had a non-atherogenic lipoprotein phenotype A. Identification of the specific lipoprotein phenotype and a quantitative analysis of small dense LDL was performed by an electrophoresis method on polyacrylamide gel (PAG), using the Lipoprint LDL system. For a quantitative analysis of HDL subclasses, i.e., large HDL, intermediatete HDL, and small HDL, in subjects with newly diagnosed cardiovascular diseases (arterial hypertension and coronary heart disease), and in subjects with a non-atherogenic hypercholesterolemia (hyper-betalipoproteinemia LDL1,2), we used an innovative electrophoresis method on polyacrylamide gel (PAG), the Lipoprint HDL system. With regard to lipids, total cholesterol and triglycerides in plasma were analyzed by an enzymatic CHOD PAP method. A control group consisted of a group of healthy normolipidemic volunteers without signs of clinically manifested impairment of the cardiovascular system. In the patient group with the diagnosis of arterial hypertension (pdisease (pcardiovascular diseases), the large

  16. A biochemical fluorometric method for assessing the oxidative properties of HDL[S

    Science.gov (United States)

    Kelesidis, Theodoros; Currier, Judith S.; Huynh, Diana; Meriwether, David; Charles-Schoeman, Christina; Reddy, Srinivasa T.; Fogelman, Alan M.; Navab, Mohamad; Yang, Otto O.

    2011-01-01

    Most current assays of HDL functional properties are cell-based. We have developed a fluorometric biochemical assay based on the oxidation of dihydrorhodamine 123 (DHR) by HDL. This cell-free assay assesses the intrinsic ability of HDL to be oxidized by measuring increasing fluorescence due to DHR oxidation over time. The assay distinguishes the oxidative potential of HDL taken from different persons, and the results are reproducible. Direct comparison of this measurement correlated well with results obtained using a validated cell-based assay (r2 = 0.62, P HDL that is applicable to large-scale clinical studies. PMID:21957198

  17. Temporal Stability of the Velodyne HDL-64E S2 Scanner for High Accuracy Scanning Applications

    Directory of Open Access Journals (Sweden)

    Craig Glennie

    2011-03-01

    Full Text Available The temporal stability and static calibration and analysis of the Velodyne HDL‑64E S2 scanning LiDAR system is discussed and analyzed. The mathematical model for measurements for the HDL-64E S2 scanner is updated to include misalignments between the angular encoder and scanner axis of rotation, which are found to be a marginally significant source of error. It is reported that the horizontal and vertical laser offsets cannot reliably be obtained with the current calibration model due to their high correlation with the horizontal and vertical offsets. By analyzing observations from two separate HDL-64E S2 scanners it was found that the temporal stability of the horizontal angle offset is near the quantization level of the encoder, but the vertical angular offset, distance offset and distance scale are slightly larger than expected. This is felt to be due to long term variations in the scanner range, whose root cause is as of yet unidentified. Nevertheless, a temporally averaged calibration dataset for each of the scanners resulted in a 25% improvement in the 3D planar misclosure residual RMSE over the standard factory calibration model.

  18. Bile acids reduce endocytosis of high-density lipoprotein (HDL) in HepG2 cells.

    Science.gov (United States)

    Röhrl, Clemens; Eigner, Karin; Fruhwürth, Stefanie; Stangl, Herbert

    2014-01-01

    High-density lipoprotein (HDL) transports lipids to hepatic cells and the majority of HDL-associated cholesterol is destined for biliary excretion. Cholesterol is excreted into the bile directly or after conversion to bile acids, which are also present in the plasma as they are effectively reabsorbed through the enterohepatic cycle. Here, we provide evidence that bile acids affect HDL endocytosis. Using fluorescent and radiolabeled HDL, we show that HDL endocytosis was reduced in the presence of high concentrations of taurocholate, a natural non-cell-permeable bile acid, in human hepatic HepG2 and HuH7 cells. In contrast, selective cholesteryl-ester (CE) uptake was increased. Taurocholate exerted these effects extracellularly and independently of HDL modification, cell membrane perturbation or blocking of endocytic trafficking. Instead, this reduction of endocytosis and increase in selective uptake was dependent on SR-BI. In addition, cell-permeable bile acids reduced HDL endocytosis by farnesoid X receptor (FXR) activation: chenodeoxycholate and the non-steroidal FXR agonist GW4064 reduced HDL endocytosis, whereas selective CE uptake was unaltered. Reduced HDL endocytosis by FXR activation was independent of SR-BI and was likely mediated by impaired expression of the scavenger receptor cluster of differentiation 36 (CD36). Taken together we have shown that bile acids reduce HDL endocytosis by transcriptional and non-transcriptional mechanisms. Further, we suggest that HDL endocytosis and selective lipid uptake are not necessarily tightly linked to each other.

  19. The application of multiple reaction monitoring and multi-analyte profiling to HDL proteins

    Science.gov (United States)

    2014-01-01

    Background HDL carries a rich protein cargo and examining HDL protein composition promises to improve our understanding of its functions. Conventional mass spectrometry methods can be lengthy and difficult to extend to large populations. In addition, without prior enrichment of the sample, the ability of these methods to detect low abundance proteins is limited. Our objective was to develop a high-throughput approach to examine HDL protein composition applicable to diabetes and cardiovascular disease (CVD). Methods We optimized two multiplexed assays to examine HDL proteins using a quantitative immunoassay (Multi-Analyte Profiling- MAP) and mass spectrometric-based quantitative proteomics (Multiple Reaction Monitoring-MRM). We screened HDL proteins using human xMAP (90 protein panel) and MRM (56 protein panel). We extended the application of these two methods to HDL isolated from a group of participants with diabetes and prior cardiovascular events and a group of non-diabetic controls. Results We were able to quantitate 69 HDL proteins using MAP and 32 proteins using MRM. For several common proteins, the use of MRM and MAP was highly correlated (p HDL. On the other hand, MRM allowed the examination of several HDL proteins not available by MAP. Conclusions MAP and MRM offer a sensitive and high-throughput approach to examine changes in HDL proteins in diabetes and CVD. This approach can be used to measure the presented HDL proteins in large clinical studies. PMID:24397693

  20. HDL-apoA-I Exchange: Rapid Detection and Association with Atherosclerosis

    Science.gov (United States)

    Borja, Mark S.; Zhao, Lei; Hammerson, Bradley; Tang, Chongren; Yang, Richard; Carson, Nancy; Fernando, Gayani; Liu, Xiaoqin; Budamagunta, Madhu S.; Genest, Jacques; Shearer, Gregory C.; Duclos, Franck; Oda, Michael N.

    2013-01-01

    High density lipoprotein (HDL) cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR) to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease. PMID:24015188

  1. Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation.

    Science.gov (United States)

    Curcic, Sanja; Holzer, Michael; Pasterk, Lisa; Knuplez, Eva; Eichmann, Thomas O; Frank, Saša; Zimmermann, Robert; Schicho, Rudolf; Heinemann, Akos; Marsche, Gunther

    2017-08-14

    Levels of secretory phospholipases A2 (sPLA2) highly increase under acute and chronic inflammatory conditions. sPLA2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, pharmacological inhibition of sPLA2 in patients with acute coronary syndrome was associated with an increased risk of myocardial infarction and stroke. Given that platelets are key players in thrombosis and inflammation, we hypothesized that sPLA2-induced hydrolysis of HDL-associated phospholipids (sPLA2-HDL) generates modified HDL particles that affect platelet function. We observed that sPLA2-HDL potently and rapidly inhibited platelet aggregation induced by several agonists, P-selectin expression, GPIIb/IIIa activation and superoxide production, whereas native HDL showed little effects. sPLA2-HDL suppressed the agonist-induced rise of intracellular Ca(2+) levels and phosphorylation of Akt and ERK1/2, which trigger key steps in promoting platelet activation. Importantly, sPLA2 in the absence of HDL showed no effects, whereas enrichment of HDL with lysophosphatidylcholines containing saturated fatty acids (the main sPLA2 products) mimicked sPLA2-HDL activities. Our findings suggest that sPLA2 generates lysophosphatidylcholine-enriched HDL particles that modulate platelet function under inflammatory conditions.

  2. Oxidative modification and poor protective activity of HDL on LDL oxidation in thalassemia.

    Science.gov (United States)

    Unchern, Supeenun; Laohareungpanya, Narumon; Sanvarinda, Yupin; Pattanapanyasat, Kovit; Tanratana, Pansakorn; Chantharaksri, Udom; Sibmooh, Nathawut

    2010-07-01

    Oxidative modification of low-density lipoprotein (LDL) has been reported in thalassemia, which is a consequence of oxidative stress. However, the levels of oxidized high-density lipoprotein (HDL) in thalassemia have not been evaluated and it is unclear whether HDL oxidation may be linked to LDL oxidation. In this study, the levels of total cholesterol, iron, protein, conjugated diene (CD), lipid hydroperoxide (LOOH), and thiobarbituric acid reactive substances (TBARs) were determined in HDL from healthy volunteers and patients with beta-thalassemia intermedia with hemoglobin E (beta-thal/Hb E). The protective activity of thalassemic HDL on LDL oxidation was also investigated. The iron content of HDL(2) and HDL(3) from beta-thal/HbE patients was higher while the cholesterol content was lower than those in healthy volunteers. Thalassemic HDL(2) and HDL(3) had increased levels of lipid peroxidation markers i.e., conjugated diene, LOOH, and TBARs. Thalassemic HDL had lower peroxidase activity than control HDL and was unable to protect LDL from oxidation induced by CuSO(4). Our findings highlight the oxidative modification and poor protective activity of thalassemic HDL on LDL oxidation which may contribute to cardiovascular complications in thalassemia.

  3. HDL-apoA-I exchange: rapid detection and association with atherosclerosis.

    Directory of Open Access Journals (Sweden)

    Mark S Borja

    Full Text Available High density lipoprotein (HDL cholesterol levels are associated with decreased risk of cardiovascular disease, but not all HDL are functionally equivalent. A primary determinant of HDL functional status is the conformational adaptability of its main protein component, apoA-I, an exchangeable apolipoprotein. Chemical modification of apoA-I, as may occur under conditions of inflammation or diabetes, can severely impair HDL function and is associated with the presence of cardiovascular disease. Chemical modification of apoA-I also impairs its ability to exchange on and off HDL, a critical process in reverse cholesterol transport. In this study, we developed a method using electron paramagnetic resonance spectroscopy (EPR to quantify HDL-apoA-I exchange. Using this approach, we measured the degree of HDL-apoA-I exchange for HDL isolated from rabbits fed a high fat, high cholesterol diet, as well as human subjects with acute coronary syndrome and metabolic syndrome. We observed that HDL-apoA-I exchange was markedly reduced when atherosclerosis was present, or when the subject carries at least one risk factor of cardiovascular disease. These results show that HDL-apoA-I exchange is a clinically relevant measure of HDL function pertinent to cardiovascular disease.

  4. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    DEFF Research Database (Denmark)

    Zanoni, Paolo; Khetarpal, Sumeet A; Larach, Daniel B;

    2016-01-01

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL......-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss......-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from...

  5. Nanostructure and Oxidation Reactivity of Nascent Soot Particles in Ethylene/Pentanol Flames

    Directory of Open Access Journals (Sweden)

    Yaoyao Ying

    2017-01-01

    Full Text Available As byproducts of the combustion process of hydrocarbon fuels, soot particles are difficult to remove, and they can greatly harm human health and pollute the environment. Therefore, the formation and growth processes of the soot particles has become a study focus of researchers. In this paper, the nanostructure and oxidation reactivity of carbonaceous particles collected from ethylene inverse diffusion flames with or without the additions of three pentanol isomers (1-pentanol, 3-methyl-1-butanol, and 2-methyl-1-butanol were investigated in detail. The nanostructure and oxidation characteristics of nascent soot particles were characterized using high resolution transmission electron microscopy (HRTEM, X-ray diffractometry (XRD and thermogravimetric analysis (TGA. It was found that the nascent soot cluster of pure ethylene flame had a loose structure, while the additions of pentanol isomers made the soot agglomerates more compact and delayed the growth of graphitic structures. The pentanol isomer additions also contributed to a higher disorder of the crystallite arrangement in the soot nanostructure. According to the TGA experiments, the results showed that the addition of pentanol isomers enhanced the oxidation reactivity of soot particles, which could help to reduce soot particle emissions.

  6. Macrolide-peptide conjugates as probes of the path of travel of the nascent peptides through the ribosome.

    Science.gov (United States)

    Washington, Arren Z; Benicewicz, Derek B; Canzoneri, Joshua C; Fagan, Crystal E; Mwakwari, Sandra C; Maehigashi, Tatsuya; Dunham, Christine M; Oyelere, Adegboyega K

    2014-11-21

    Despite decades of research on the bacterial ribosome, the ribosomal exit tunnel is still poorly understood. Although it has been suggested that the exit tunnel is simply a convenient route of egress for the nascent chain, specific protein sequences serve to slow the rate of translation, suggesting some degree of interaction between the nascent peptide chain and the exit tunnel. To understand how the ribosome interacts with nascent peptide sequences, we synthesized and characterized a novel class of probe molecules. These peptide-macrolide (or "peptolide") conjugates were designed to present unique peptide sequences to the exit tunnel. Biochemical and X-ray structural analyses of the interactions between these probes and the ribosome reveal interesting insights about the exit tunnel. Using translation inhibition and RNA structure probing assays, we find the exit tunnel has a relaxed preference for the directionality (N → C or C → N orientation) of the nascent peptides. Moreover, the X-ray crystal structure of one peptolide derived from a positively charged, reverse Nuclear Localization Sequence peptide, bound to the 70S bacterial ribosome, reveals that the macrolide ring of the peptolide binds in the same position as other macrolides. However, the peptide tail folds over the macrolide ring, oriented toward the peptidyl transferase center and interacting in a novel manner with 23S rRNA residue C2442 and His69 of ribosomal protein L4. These data suggest that these peptolides are viable probes for interrogating nascent peptide-exit tunnel interaction.

  7. Toward a better understanding of the mechanisms of symbiosis: a comprehensive proteome map of a nascent insect symbiont

    Directory of Open Access Journals (Sweden)

    François Renoz

    2017-05-01

    Full Text Available Symbiotic bacteria are common in insects and can affect various aspects of their hosts’ biology. Although the effects of insect symbionts have been clarified for various insect symbiosis models, due to the difficulty of cultivating them in vitro, there is still limited knowledge available on the molecular features that drive symbiosis. Serratia symbiotica is one of the most common symbionts found in aphids. The recent findings of free-living strains that are considered as nascent partners of aphids provide the opportunity to examine the molecular mechanisms that a symbiont can deploy at the early stages of the symbiosis (i.e., symbiotic factors. In this work, a proteomic approach was used to establish a comprehensive proteome map of the free-living S. symbiotica strain CWBI-2.3T. Most of the 720 proteins identified are related to housekeeping or primary metabolism. Of these, 76 were identified as candidate proteins possibly promoting host colonization. Our results provide strong evidence that S. symbiotica CWBI-2.3T is well-armed for invading insect host tissues, and suggest that certain molecular features usually harbored by pathogenic bacteria are no longer present. This comprehensive proteome map provides a series of candidate genes for further studies to understand the molecular cross-talk between insects and symbiotic bacteria.

  8. Serum TC/HDL-C,TG/HDL-C and LDL-C/HDL-C in predicting the risk of myocardial infarction in normolipidae-mic patients in South Asia:A case-control study

    Institute of Scientific and Technical Information of China (English)

    Arun Kumar; Ramiah Sivakanesan

    2008-01-01

    Dyslipidemia the major cause of atherosclerosis are suggested to act synergistically with non-lipid risk factors to increase atherogenesis.Low-density lipoprotein cholesterol (LDL-C)is the main therapeutic target in the pre-vention of CVD.Increased triglycerides (TG)and decreased high-density lipoprotein (LDL-C)are considered to be a major risk factor for the development of insulin resistant and metabolic syndrome.Although the TG/HDL-C ratio has been used in recent studies as a clinical indicator for insulin resistance,results were inconsis-tent.The TG/HDL-C ratio is also widely used to assess the lipid atherogenesis.How ever the utility of this rate for predicting coronary heart disease (CHD)risk is not clear.We encountered myocardial infarct patients with normal serum lipid concentration so this study was undertaken to evaluate the usefulness of these lipid ratios in predicting CHD risk in normolipidemic AMI patients and to compare the results with healthy subjects.The aim of the present study was to evaluate serum TC/HDL-C,TG/HDL-C and LDL-C/HDL-C in myocardial infarct subjects with normal lipid profile.To study this,lipid profile was determined in 165 normolipidemic acute myo-cardial infarction patients and 165 age/sex-matched controls.Total cholesterol,triglycerides,and HDL-cho-lesterol were analyzed enzymatically using kits obtained from Randox Laboratories Limited,Crumlin,UK. Plasma LDL-cholesterol was determined from the values of total cholesterol and HDL- cholesterol using the friedwalds formula.The values were expressed as means ± standard deviation (SD)and data from patients and controls was compared using students't'-test.The results and conclusion of the study were:Total cholester-ol,TC:HDL-C ratio,triglycerides,LDL-cholesterol,LDL:HDL-C ratio were higher in MI patients (p<0. 001).HDL-C concentration was significantly lower in MI patients than controls (p<0.001).Higher ratio of TC/HDL-C,TG/HDL-C and LDL-C/HDL-C was observed in AMI patients compared

  9. In vivo triglyceride synthesis in subcutaneous adipose tissue of humans correlates with plasma HDL parameters

    Science.gov (United States)

    Tuvdendorj, Demidmaa; Munoz, Alejandro O.; Ruiz-Barros, Viviana; Schwarz, Jean-Marc; Montalto, Giuseppe; Chandalia, Manisha; Sowers, Lawrence C.; Rizzo, Manfredi; Murphy, Elizabeth J; Abate, Nicola

    2016-01-01

    Backgrounds and aims Low concentrations of plasma HDL-C are associated with the development of atherosclerotic cardiovascular diseases and type 2 diabetes. Here we aimed to explore the relationship between the in vivo fractional synthesis of triglycerides (fTG) in subcutaneous (s.q.) abdominal adipose tissue (AT), HDL-C concentrations and HDL particle size composition in non-diabetic humans. Methods The fTG in s.q. abdominal AT was measured in 16 non-diabetic volunteers (7 women, 9 men; Age: 49±20 years; BMI: 31±5 kg/m; Fasting Plasma Glucose: 90±10 mg/dl) after 2H2O labeling. HDL-C concentration and subclasses, large (L-HDL), intermediate (I-HDL) and small (S-HDL) were measured. Results Linear regression analyses demonstrated significant associations of fTG with plasma concentration of HDL-C (r=0.625,p=0.009) and percent contribution of L-HDL (r=0.798,pHDL (r=−0.765,pHDL (r=−0.629, p=0.009). When analyses were performed by gender, the associations remained significant in women (HDL-C: r=0.822,p=0.023; L-HDL: r=0.892,p=0.007; I-HDL: r=−0.927,p=0.003) but not men. Conclusions Our study demonstrated an in vivo association between subcutaneous abdominal adipose tissue lipid dynamics and HDL parameters in humans, but this was true for women not men. Positive association with L-HDL and negative with I-HDL suggest that subcutaneous abdominal adipose tissue lipid dynamics may play an important role in production of mature functional HDL particles. Further studies evaluating the mechanism responsible for these associations and the observed gender differences are important and warranted to identify potential novel targets of intervention to increase the production of atheroprotective subclasses of HDL-Cs and thus decreasing the risks of development of atherosclerotic conditions. PMID:27323227

  10. The HDL anti-inflammatory function is impaired in myocardial infarction and may predict new cardiac events independent of HDL cholesterol

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Annema, Wijtske; Tio, Rene A.; Tietge, Uwe J. F.

    2014-01-01

    Background: Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiologically important for atheroprotection. We compared the HDL anti-inflammatory capacity between patients with acute myocardial infarction (MI) and patients with non-cardiac chest pain, and pros

  11. The HDL anti-inflammatory function is impaired in myocardial infarction and may predict new cardiac events independent of HDL cholesterol

    NARCIS (Netherlands)

    Dullaart, Robin P. F.; Annema, Wijtske; Tio, Rene A.; Tietge, Uwe J. F.

    2014-01-01

    Background: Intrinsic functional properties of high density lipoproteins (HDL) are considered to be physiologically important for atheroprotection. We compared the HDL anti-inflammatory capacity between patients with acute myocardial infarction (MI) and patients with non-cardiac chest pain, and

  12. Low HDL cholesterol, aggression and altered central serotonergic activity.

    Science.gov (United States)

    Buydens-Branchey, L; Branchey, M; Hudson, J; Fergeson, P

    2000-03-01

    Many studies support a significant relation between low cholesterol levels and poor impulse, aggression and mood control. Evidence exists also for a causal link between low brain serotonin (5-HT) activity and these behaviors. Mechanisms linking cholesterol and hostile or self-destructive behavior are unknown, but it has been suggested that low cholesterol influences 5-HT function. This study was designed to explore the relationship between plasma cholesterol, measures of impulsivity and aggression, and indices of 5-HT function in personality disordered cocaine addicts. Thirty-eight hospitalized male patients (age 36.8+/-7.1) were assessed with the DSM-III-R, the Buss-Durkee Hostility Inventory (BDHI), the Barratt Impulsiveness Scale (BIS) and the Brown-Goodwin Assessment for Life History of Aggression. Fasting basal cholesterol (total, LDL and HDL) was determined 2 weeks after cocaine discontinuation. On the same day 5-HT function was assessed by neuroendocrine (cortisol and prolactin) and psychological (NIMH and 'high' self-rating scales) responses following meta-chlorophenylpiperazine (m-CPP) challenges. Reduced neuroendocrine responses, 'high' feelings and increased 'activation-euphoria' following m-CPP have been interpreted as indicating 5-HT alterations in a variety of psychiatric conditions. Significantly lower levels of HDL cholesterol were found in patients who had a history of aggression (P=0.005). Lower levels of HDL cholesterol were also found to be significantly associated with more intense 'high' and 'activation-euphoria' responses as well as with blunted cortisol responses to m-CPP (P=0.033, P=0.025 and P=0.018, respectively). This study gives further support to existing evidence indicating that in some individuals, the probability of exhibiting impulsive and violent behaviors may be increased when cholesterol is low. It also suggests that low cholesterol and alterations in 5-HT activity may be causally related.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-08-01

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

  14. Excess Cdt1 inhibits nascent strand elongation by repressing the progression of replication forks in Xenopus egg extracts.

    Science.gov (United States)

    Nakazaki, Yuta; Tsuyama, Takashi; Seki, Masayuki; Takahashi, Mikiko; Enomoto, Takemi; Tada, Shusuke

    2016-02-01

    Cdt1 is a protein essential for initiation of DNA replication; it recruits MCM helicase, a core component of the replicative DNA helicase, onto replication origins. In our previous study, we showed that addition of excess Cdt1 inhibits nascent strand elongation during DNA replication in Xenopus egg extracts. In the present study, we investigated the mechanism behind the inhibitory effect of Cdt1. We found that addition of recombinant Cdt1 inhibited nascent DNA synthesis in a reinitiation-independent manner. To identify the mechanism by which Cdt1 inhibits nascent strand elongation, the effect of Cdt1 on loading of Mcm4 and Rpa70 onto chromatin was examined. The results showed that Cdt1 suppressed the excessive Rpa70 binding caused by extensive, aphidicolin-induced DNA unwinding; this unwinding occurs between stalled DNA polymerases and advancing replication forks. These findings suggested that excess Cdt1 suppressed the progression of replication forks.

  15. Monitoring the spatiotemporal dynamics of proteins at replication forks and in assembled chromatin using isolation of proteins on nascent DNA.

    Science.gov (United States)

    Sirbu, Bianca M; Couch, Frank B; Cortez, David

    2012-03-01

    Understanding the processes of DNA replication, chromatin assembly and maturation, and the replication stress response requires the ability to monitor protein dynamics at active and damaged replication forks. Detecting protein accumulation at replication forks or damaged sites has primarily relied on immunofluorescence imaging, which is limited in resolution and antibody sensitivity. Here we describe a procedure to isolate proteins on nascent DNA (iPOND) that permits a high-resolution spatiotemporal analysis of proteins at replication forks or on chromatin following DNA replication in cultured cells. iPOND relies on labeling of nascent DNA with the nucleoside analog 5-ethynyl-2'-deoxyuridine (EdU). Biotin conjugation to EdU-labeled DNA using click chemistry facilitates a single-step streptavidin purification of proteins bound to the nascent DNA. iPOND permits an interrogation of any cellular process linked to DNA synthesis using a 3- to 4-d protocol.

  16. Static Calibration and Analysis of the Velodyne HDL-64E S2 for High Accuracy Mobile Scanning

    Directory of Open Access Journals (Sweden)

    Craig Glennie

    2010-06-01

    Full Text Available The static calibration and analysis of the Velodyne HDL-64E S2 scanning LiDAR system is presented and analyzed. The mathematical model for measurements for the HDL-64E S2 scanner is derived and discussed. A planar feature based least squares adjustment approach is presented and utilized in a minimally constrained network in order to derive an optimal solution for the laser’s internal calibration parameters. Finally, the results of the adjustment along with a detailed examination of the adjustment residuals are given. A three-fold improvement in the planar misclosure residual RMSE over the standard factory calibration model was achieved by the proposed calibration. Results also suggest that there may still be some unmodelled distortions in the range measurements from the scanner. However, despite this, the overall precision of the adjusted laser scanner data appears to make it a viable choice for high accuracy mobile scanning applications.

  17. High density lipoprotein (HDL) reverses palmitic acid induced energy metabolism imbalance by switching CD36 and GLUT4 signaling pathways in cardiomyocyte.

    Science.gov (United States)

    Wen, Su-Ying; Velmurugan, Bharath Kumar; Day, Cecilia Hsuan; Shen, Chia-Yao; Chun, Li-Chin; Tsai, Yi-Chieh; Lin, Yueh-Min; Chen, Ray-Jade; Kuo, Chia-Hua; Huang, Chih-Yang

    2017-11-01

    In our previous study palmitic acid (PA) induced lipotoxicity and switches energy metabolism from CD36 to GLUT4 in H9c2 cells. Low level of high density lipoprotein (HDL) is an independent risk factor for cardiac hypertrophy. Therefore, we in the present study investigated whether HDL can reverse PA induced lipotoxicity in H9c2 cardiomyoblast cells. In this study, we treated H9c2 cells with PA to create a hyperlipidemia model in vitro and analyzed for CD36 and GLUT4 metabolic pathway proteins. CD36 metabolic pathway proteins (phospho-AMPK, SIRT1, PGC1α, PPARα, CPT1β, and CD36) were decreased by high PA (150 and 200 μg/μl) concentration. Interestingly, expression of GLUT4 metabolic pathway proteins (p-PI3K and pAKT) were increased at low concentration (50 μg/μl) and decreased at high PA concentration. Whereas, phospho-PKCζ, GLUT4 and PDH proteins expression was increased in a dose dependent manner. PA treated H9c2 cells were treated with HDL and analyzed for cell viability. Results showed that HDL treatment induced cell proliferation efficiency in PA treated cells. In addition, HDL reversed the metabolic effects of PA: CD36 translocation was increased and reduced GLUT4 translocation, but HDL treatment significantly increased CD36 metabolic pathway proteins and reduced GLUT4 pathway proteins. Rat neonatal cardiomyocytes showed similar results. In conclusion, HDL reversed palmatic acid-induced lipotoxicity and energy metabolism imbalance in H9c2 cardiomyoblast cells and in neonatal rat cardiomyocyte cells. © 2017 Wiley Periodicals, Inc.

  18. Association of serum triglyceride-to-HDL cholesterol ratio with carotid artery intima-media thickness, insulin resistance and nonalcoholic fatty liver disease in children and adolescents.

    Science.gov (United States)

    Pacifico, L; Bonci, E; Andreoli, G; Romaggioli, S; Di Miscio, R; Lombardo, C V; Chiesa, C

    2014-07-01

    The triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C) ratio has been reported as a useful marker of atherogenic lipid abnormalities, insulin resistance, and cardiovascular disease. We evaluated in a large sample of children and adolescents the association of TG/HDL-C ratio with early signs of morphological vascular changes and cardiometabolic risk factors including nonalcoholic fatty liver disease (NAFLD). The study population, including 548 children (aged 6-16 years), of whom 157 were normal-weight, 118 overweight, and 273 obese, had anthropometric, laboratory, liver and carotid ultrasonography (carotid artery intima-media thickness-cIMT) data collected. Subjects were stratified into tertiles of TG/HDL-C. There was a progressive increase in body mass index (BMI), BMI-SD score (SDS), waist circumference, blood pressure (BP), liver enzymes, glucose, insulin, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein (hsCRP), and cIMT values across TG/HDL-C tertiles. The odds ratios for central obesity, insulin resistance, high hsCRP, NAFLD, metabolic syndrome, and elevated cIMT increased significantly with the increasing tertile of TG/HDL-C ratio, after adjustment for age, gender, pubertal status, and BMI-SDS. In a stepwise multivariate logistic regression analysis, increased cIMT was associated with high TG/HDL-C ratio [OR, 1.81 (95% CI, 1.08-3.04); P < 0.05], elevated BP [5.13 (95% CI, 1.03-15.08); P < 0.05], insulin resistance [2.16 (95% CI, 1.30-3.39); P < 0.01], and NAFLD [2.70 (95% CI, 1.62-4.56); P < 0.01]. TG/HDL-C ratio may help identify children and adolescents at high risk for structural vascular changes and metabolic derangement. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Apolipoprotein M predicts pre-beta-HDL formation: studies in type 2 diabetic and nondiabetic subjects

    DEFF Research Database (Denmark)

    Plomgaard, P; Dullaart, R P F; de Vries, R;

    2009-01-01

    OBJECTIVE: Studies in mice suggest that plasma apoM is lowered in hyperinsulinaemic diabetes and that apoM stimulates formation of pre-beta-HDL. Pre-beta-HDL is an acceptor of cellular cholesterol and may be critical for reverse cholesterol transport. Herein, we examined whether patients with type...... 2 diabetes have reduced plasma apoM and whether apoM is associated with pre-beta-HDL formation and cellular cholesterol efflux. DESIGN: In 78 patients with type 2 diabetes and 89 control subjects, we measured plasma apoM with ELISA, pre-beta-HDL and pre-beta-HDL formation, phospholipid transfer...... to diabetes-associated obesity. ApoM was positively related to both HDL (r = 0.16; P = 0.04) and LDL cholesterol (r = 0.28; P = 0.0003). Pre-beta-HDL and pre-beta-HDL formation were not different between diabetic and control subjects. ApoM predicted pre-beta-HDL (r = 0.16; P = 0.04) and pre-beta-HDL formation...

  20. Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease.

    Science.gov (United States)

    Srivastava, Rai Ajit K

    2017-08-21

    Coronary artery disease, the leading cause of death in the developed and developing countries, is prevalent in diabetes mellitus with 68% cardiovascular disease (CVD)-related mortality. Epidemiological studies suggested inverse correlation between HDL and CVD occurrence. Therefore, low HDL concentration observed in diabetic patients compared to non-diabetic individuals was thought to be one of the primary causes of increased risks of CVD. Efforts to raise HDL level via CETP inhibitors, Torcetrapib and Dalcetrapib, turned out to be disappointing in outcome studies despite substantial increases in HDL-C, suggesting that factors beyond HDL concentration may be responsible for the increased risks of CVD. Therefore, recent studies have focused more on HDL function than on HDL levels. The metabolic environment in diabetes mellitus condition such as hyperglycemia-induced advanced glycation end products, oxidative stress, and inflammation promote HDL dysfunction leading to greater risks of CVD. This review discusses dysfunctional HDL as one of the mechanisms of increased CVD risks in diabetes mellitus through adversely affecting components that support HDL function in cholesterol efflux and LDL oxidation. The dampening of reverse cholesterol transport, a key process that removes cholesterol from lipid-laden macrophages in the arterial wall, leads to increased risks of CVD in diabetic patients. Therapeutic approaches to keep diabetes under control may benefit patients from developing CVD.

  1. Novel rare mutations and promoter haplotypes in ABCA1 contribute to low-HDL-C levels.

    Science.gov (United States)

    Slatter, T L; Jones, G T; Williams, M J A; van Rij, A M; McCormick, S P A

    2008-02-01

    The ATP-binding cassette A1 (ABCA1) protein regulates plasma high-density lipoprotein (HDL) levels. Mutations in ABCA1 can cause HDL deficiency and increase the risk of premature coronary artery disease. Single nucleotide polymorphisms (SNPs) in ABCA1 are associated with variation in plasma HDL levels. We investigated the prevalence of mutations and common SNPs in ABCA1 in 154 low-HDL individuals and 102 high-HDL individuals. Mutations were identified in five of the low-HDL subjects, three having novel variants (I659V, R2004K, and A2028V) and two with a previously identified variant (R1068H). Analysis of four SNPs in the ABCA1 gene promoter (C-564T, G-407C, G-278C, and C-14T) identified the C-14T SNP and the TCCT haplotype to be over-represented in low-HDL individuals. The R1587K SNP was over-represented in low-HDL individuals, and the V825I and I883M SNPs over-represented in high-HDL individuals. We conclude that sequence variation in ABCA1 contributes significantly to variation in HDL levels.

  2. Dalcetrapib and anacetrapib differently impact HDL structure and function in rabbits and monkeys.

    Science.gov (United States)

    Brodeur, Mathieu R; Rhainds, David; Charpentier, Daniel; Mihalache-Avram, Teodora; Mecteau, Mélanie; Brand, Geneviève; Chaput, Evelyne; Perez, Anne; Niesor, Eric J; Rhéaume, Eric; Maugeais, Cyrille; Tardif, Jean-Claude

    2017-07-01

    Inhibition of cholesteryl ester transfer protein (CETP) increases HDL cholesterol (HDL-C) levels. However, the circulating CETP level varies and the impact of its inhibition in species with high CETP levels on HDL structure and function remains poorly characterized. This study investigated the effects of dalcetrapib and anacetrapib, the two CETP inhibitors (CETPis) currently being tested in large clinical outcome trials, on HDL particle subclass distribution and cholesterol efflux capacity of serum in rabbits and monkeys. New Zealand White rabbits and vervet monkeys received dalcetrapib and anacetrapib. In rabbits, CETPis increased HDL-C, raised small and large α-migrating HDL, and increased ABCA1-induced cholesterol efflux. In vervet monkeys, although anacetrapib produced similar results, dalcetrapib caused opposite effects because the LDL-C level was increased by 42% and HDL-C decreased by 48% (P HDL were reduced by 16% (P HDL in vivo and consequently the cholesterol efflux capacity. The opposite effects of dalcetrapib in different species indicate that its impact on HDL metabolism could vary greatly according to the metabolic environment. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  3. Plasma cholesterol homeostasis, HDL remodeling and function during the acute phase reaction.

    Science.gov (United States)

    Zimetti, Francesca; De Vuono, Stefano; Gomaraschi, Monica; Adorni, Maria Pia; Favari, Elda; Ronda, Nicoletta; Ricci, Maria Anastasia; Veglia, Fabrizio; Calabresi, Laura; Lupattelli, Graziana

    2017-10-01

    Acute phase reaction (APR) is a systemic inflammation triggered by several conditions associated with lipid profile alterations. We evaluated whether APR also associates with changes in cholesterol synthesis and absorption, HDL structure, composition, and cholesterol efflux capacity (CEC). We analyzed 59 subjects with APR related to infections, oncologic causes, or autoimmune diseases and 39 controls. We detected no difference in markers of cholesterol synthesis and absorption. Conversely, a significant reduction of LpA-I- and LpAI:AII-containing HDL (-28% and -44.8%, respectively) and of medium-sized HDL (-10.5%) occurred in APR. Total HDL CEC was impaired in APR subjects (-18%). Evaluating specific CEC pathways, we found significant reductions in CEC by aqueous diffusion and by the transporters scavenger receptor B-I and ABCG1 (-25.5, -41.1 and -30.4%, respectively). ABCA1-mediated CEC was not affected. Analyses adjusted for age and gender provided similar results. In addition, correcting for HDL-cholesterol (HDL-C) levels, the differences in aqueous diffusion total and ABCG1-CEC remained significant. APR subjects displayed higher levels of HDL serum amyloid A (+20-folds; P = 0.003). In conclusion, APR does not associate with cholesterol synthesis and absorption changes but with alterations of HDL composition and a marked impairment of HDL CEC, partly independent of HDL-C serum level reduction. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  4. Pleiotropic effects of apolipoprotein C3 on HDL functionality and adipose tissue metabolic activity.

    Science.gov (United States)

    Zvintzou, Evangelia; Lhomme, Marie; Chasapi, Stella; Filou, Serafoula; Theodoropoulos, Vassilis; Xapapadaki, Eva; Kontush, Anatol; Spyroulias, George; Tellis, Constantinos C; Tselepis, Alexandros D; Constantinou, Caterina; Kypreos, Kyriakos E

    2017-09-01

    APOC3 is produced mainly by the liver and intestine and approximately half of plasma APOC3 associates with HDL. Though it was believed that APOC3 associates with HDL by simple binding to preexisting particles, recent data support that biogenesis of APOC3-containing HDL (APOC3-HDL) requires Abca1. Moreover, APOC3-HDL contributes to plasma triglyceride homeostasis by preventing APOC3 association with triglyceride-rich lipoproteins. Interestingly, APOC3-HDL also shows positive correlation with the morbidly obese phenotype. However, the roles of APOC3 in HDL functionality and adipose tissue metabolic activity remain unknown. Therefore, here we investigated the direct effects of APOC3 expression on HDL structure and function, as well as white adipose tissue (WAT) and brown adipose tissue (BAT) metabolic activity. C57BL/6 mice were infected with an adenovirus expressing human APOC3 or a recombinant attenuated control adenovirus expressing green fluorescent protein and blood and tissue samples were collected at 5 days postinfection. HDL was then analyzed for its apolipoprotein and lipid composition and particle functionality. Additionally, purified mitochondria from BAT and WAT were analyzed for uncoupling protein 1, cytochrome c (Cytc), and Cytc oxidase subunit 4 protein levels as an indirect measure of their metabolic activity. Serum metabolomic analysis was performed by NMR. Combined, our data show that APOC3 modulates HDL structure and function, while it selectively promotes BAT metabolic activation. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Evaluation of CETP activity in vivo under non-steady-state conditions: influence of anacetrapib on HDL-TG flux[S

    Science.gov (United States)

    McLaren, David G.; Previs, Stephen F.; Phair, Robert D.; Stout, Steven J.; Xie, Dan; Chen, Ying; Salituro, Gino M.; Xu, Suoyu S.; Castro-Perez, Jose M.; Opiteck, Gregory J.; Akinsanya, Karen O.; Cleary, Michele A.; Dansky, Hayes M.; Johns, Douglas G.; Roddy, Thomas P.

    2016-01-01

    Studies in lipoprotein kinetics almost exclusively rely on steady-state approaches to modeling. Herein, we have used a non-steady-state experimental design to examine the role of cholesteryl ester transfer protein (CETP) in mediating HDL-TG flux in vivo in rhesus macaques, and therefore, we developed an alternative strategy to model the data. Two isotopomers ([2H11] and [13C18]) of oleic acid were administered (orally and intravenously, respectively) to serve as precursors for labeling TGs in apoB-containing lipoproteins. The flux of a specific TG (52:2) from these donor lipoproteins to HDL was used as the measure of CETP activity; calculations are also presented to estimate total HDL-TG flux. Based on our data, we estimate that the peak total postprandial TG flux to HDL via CETP is ∼13 mg·h−1·kg−1 and show that this transfer was inhibited by 97% following anacetrapib treatment. Collectively, these data demonstrate that HDL TG flux can be used as a measure of CETP activity in vivo. The fact that the donor lipoproteins can be labeled in situ using well-established stable isotope tracer techniques suggests ways to measure this activity for native lipoproteins in free-living subjects under any physiological conditions. PMID:26658238

  6. Qualidade microbiológica da água de algumas nascentes de Muzambinho/MG

    Directory of Open Access Journals (Sweden)

    Marisa Donizetti Passos Barbieri

    2013-07-01

    Full Text Available A água é o elemento essencial à manutenção da vida, para que esta possa ser consumida sem apresentar riscos à saúde e bem estar de seres humanos e outros animais deve apresentar padrões de potabilidade, caso isto não ocorra há eminente perigo de conter agentes prejudiciais. Este estudo teve por objetivo avaliar a potabilidade da água ou nascentes situadas ao norte do município de muzambinho-MG, também visou analisar o nível de poluição de um importante rio presente na mesma cidade. E através de uma comparação de amostras de água coletada em caixa d`água e diretamente das tubulações da Companhia de tratamento de água (COPASA direcionou sobre os cuidados necessários por parte dos moradores com as caixas d`agua. Para que a água tratada não venha a ser contaminada por falta de limpeza destas. Foram coletadas 37 amostras ao todo, sendo que, as coletas nas nascentes ocorreram em diferentes estações do ano na seca (primavera e no período chuvoso (verão, no segundo período de coleta houve três repetições com intervalos de quinze dias. As coletas foram realizadas de acordo com o método de coletagem tanto para água tratada quanto para as sem tratamentos. Essas amostras foram enviadas ao laboratório de Bromatologia e Água do IFSULDEMINAS CAMPUS MUZAMBINHO, onde as análises microbiológicas de coliformes totais, fecais ou termotolerantes e contagem de placas foram realizadas. Em um trabalho com 45 amostras de água na cidade de Alfenas foi verificado que 25 amostras apresentaram-se impróprias para o consumo humano em relação a bactérias heterotróficas que poderiam vir a apresentar riscos a saúde do consumidor. Os resultado obtidos com a maioria das análises não estão dentro das normativas estabelecidas pela portaria nº 2.914/2011 do Ministério da saúde, ou seja, impróprias para o consumo humano apresentado considerável risco a saúde. Palavras chaves: água, potabilidade, contaminação, nascentes.

  7. Historical milestones in measurement of HDL-cholesterol: impact on clinical and laboratory practice.

    Science.gov (United States)

    Langlois, Michel R; Blaton, Victor H

    2006-07-23

    High-density lipoprotein cholesterol (HDL-C) comprises a family of particles with differing physicochemical characteristics. Continuing progress in improving HDL-C analysis has originated from two separate fields-one clinical, reflecting increased attention to HDL-C in estimating risk for coronary heart disease (CHD), and the other analytical, reflecting increased emphasis on finding more reliable and cost-effective HDL-C assays. Epidemiologic and prospective studies established the inverse association of HDL-C with CHD risk, a relationship that is consistent with protective mechanisms demonstrated in basic research and animal studies. Atheroprotective and less atheroprotective HDL subpopulations have been described. Guidelines on primary and secondary CHD prevention, which increased the workload in clinical laboratories, have led to a revolution in HDL-C assay technology. Many analytical techniques including ultracentrifugation, electrophoresis, chromatography, and polyanion precipitation methods have been developed to separate and quantify HDL-C and HDL subclasses. More recently developed homogeneous assays enable direct measurement of HDL-C on an automated analyzer, without the need for manual pretreatment to separate non-HDL. Although homogeneous assays show improved accuracy and precision in normal serum, discrepant results exist in samples with atypical lipoprotein characteristics. Hypertriglyceridemia and monoclonal paraproteins are important interfering factors. A novel approach is nuclear magnetic resonance spectroscopy that allows rapid and reliable analysis of lipoprotein subclasses, which may improve the identification of individuals at increased CHD risk. Apolipoprotein A-I, the major protein of HDL, has been proposed as an alternative cardioprotective marker avoiding the analytical limitations of HDL-C.

  8. Avaliação qualitativa da água de nascentes com diferentes usos do solo em seu entorno

    OpenAIRE

    Pinto,Lilian Vilela Andrade; Roma,Talita Nazareth de; Balieiro,Kátia Regina de Carvalho

    2012-01-01

    Alguns fatores são responsabilizados pela degradação da qualidade da água dos mananciais. Neste trabalho, objetivou-se avaliar o impacto de diferentes usos do solo sobre as propriedades físicas, químicas e biológicas da água de cinco nascentes situadas em Inconfidentes/MG. Os resultados revelaram que a nascente parcialmente protegida por vegetação nativa apresentou qualidade superior da água quanto aos parâmetros cor, turbidez, demanda bioquímica de oxigênio (DBO5), fosfato total, nitrato, ox...

  9. A VLSI Implementation of Four-Phase Lift Controller Using Verilog HDL

    Science.gov (United States)

    Kumar, Manish; Singh, Priyanka; Singh, Shesha

    2017-08-01

    With the advent of an era of staggering range of new technologies to provide ease of mobility and transportation elevators have become an essential component of all high rise buildings. An elevator is a type of vertical transportation that moves people between the floors of a high rise building. A four-Phase lift controller modeled on Verilog HDL code using Finite State Machine (FSM) has been presented in this paper. Verilog HDL helps in automated analysis and simulation of lift controller circuit. This design is based on synchronous input that operates on a fixed frequency. The Lift motion is controlled by means of accepting the destination floor level as input and generate control signal as output. In the proposed design a Verilog RTL code is developed and verified. Project Navigator of XILINX has been used as a code writing platform and results were simulated using Modelsim 5.4a simulator. This paper discusses the overall evolution of design and also discusses simulated results.

  10. HDL-related mechanisms of olive oil protection in cardiovascular disease.

    Science.gov (United States)

    Lou-Bonafonte, José M; Fitó, Montse; Covas, María-Isabel; Farràs, Marta; Osada, Jesús

    2012-07-01

    The low incidence of cardiovascular disease in countries bordering the Mediterranean basin, where olive oil is the main source of dietary fat, and the negative association between this disease with high density lipoproteins has stimulated interest. This review summarizes the current knowledge gathered from human and animal studies regarding olive oil and high density lipoproteins. Cumulative evidence suggests that high density lipoprotein (HDL) cholesterol, and its main apolipoprotein A1, may be increased by consuming olive oil when compared with carbohydrate and low fat diets in humans. Conflicting results have been found in many studies when olive oil diets were compared with other sources of fat. The role of virgin olive oil minor components on its protective effect has been demonstrated by a growing number of studies although its exact mechanism remains to be elucidated. Dietary amount of olive oil, use of virgin olive oil, cholesterol intake, and physiopathological states such as genetic background, sex, age, obesity or fatty liver are variables that may offset those effects. Further studies in this field in humans and in animal models are warranted due to the complexity of HDL particles.

  11. HSC90 is required for nascent hepatitis C virus core protein stability in yeast cells.

    Science.gov (United States)

    Kubota, Naoko; Inayoshi, Yasutaka; Satoh, Naoko; Fukuda, Takashi; Iwai, Kenta; Tomoda, Hiroshi; Kohara, Michinori; Kataoka, Kazuhiro; Shimamoto, Akira; Furuichi, Yasuhiro; Nomoto, Akio; Naganuma, Akira; Kuge, Shusuke

    2012-07-30

    Hepatitis C virus core protein (Core) contributes to HCV pathogenicity. Here, we demonstrate that Core impairs growth in budding yeast. We identify HSP90 inhibitors as compounds that reduce intracellular Core protein level and restore yeast growth. Our results suggest that HSC90 (Hsc82) may function in the protection of the nascent Core polypeptide against degradation in yeast and the C-terminal region of Core corresponding to the organelle-interaction domain was responsible for Hsc82-dependent stability. The yeast system may be utilized to select compounds that can direct the C-terminal region to reduce the stability of Core protein. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  12. Splicing of Nascent RNA Coincides with Intron Exit from RNA Polymerase II.

    Science.gov (United States)

    Carrillo Oesterreich, Fernando; Herzel, Lydia; Straube, Korinna; Hujer, Katja; Howard, Jonathon; Neugebauer, Karla M

    2016-04-01

    Protein-coding genes in eukaryotes are transcribed by RNA polymerase II (Pol II) and introns are removed from pre-mRNA by the spliceosome. Understanding the time lag between Pol II progression and splicing could provide mechanistic insights into the regulation of gene expression. Here, we present two single-molecule nascent RNA sequencing methods that directly determine the progress of splicing catalysis as a function of Pol II position. Endogenous genes were analyzed on a global scale in budding yeast. We show that splicing is 50% complete when Pol II is only 45 nt downstream of introns, with the first spliced products observed as introns emerge from Pol II. Perturbations that slow the rate of spliceosome assembly or speed up the rate of transcription caused splicing delays, showing that regulation of both processes determines in vivo splicing profiles. We propose that matched rates streamline the gene expression pathway, while allowing regulation through kinetic competition.

  13. Exonuclease-mediated degradation of nascent RNA silences genes linked to severe malaria

    DEFF Research Database (Denmark)

    Zhang, Qingfeng; Siegel, T Nicolai; Martins, Rafael M

    2014-01-01

    malaria. The mechanism determining upsA activation remains unknown. Here we show that an entirely new type of gene silencing mechanism involving an exonuclease-mediated degradation of nascent RNA controls the silencing of genes linked to severe malaria. We identify a novel chromatin......-associated exoribonuclease, termed PfRNase II, that controls the silencing of upsA var genes by marking their transcription start site and intron-promoter regions leading to short-lived cryptic RNA. Parasites carrying a deficient PfRNase II gene produce full-length upsA var transcripts and intron-derived antisense long non......-coding RNA. The presence of stable upsA var transcripts overcomes monoallelic expression, resulting in the simultaneous expression of both upsA and upsC type PfEMP1 proteins on the surface of individual infected red blood cells. In addition, we observe an inverse relationship between transcript levels of Pf...

  14. Assessment of the Effect of Gene Polymorphisms and Environmental Risk Factors on Low HDL Over Time: Tehran Lipid and Glucose Study

    Directory of Open Access Journals (Sweden)

    Mehrabi Yadollah

    2015-07-01

    Full Text Available Objective: Due to existing association between high-density lipoprotein (HDL and cardiovascular disease, detection of factors affecting this lipid is important. Environmental factors and genetic variations have an important role in HDL level. The effects of these risk factors can be time-dependent; so, study of their effects on HDL level over time is important. In this study, we used transition model to analyze binary longitudinal data to investigate single nucleotide polymorphism (SNP and other risk factors affecting low HDL over time. Materials and Methods: Data of 329 participants of 3 phases of Tehran Lipid and Glucose Study (TLGS was analyzed using marginal transition model. This model has a formulation which allows first and second order Markov dependence to take into account the correlation among successive observations of the same individual in longitudinal binary response for which the marginal probability of success is modelled via a form of logistic regression. Results: Results of first order transition model showed that the odds ratio (OR for having low HDL in women compared to men was 1.54 (95% CI: 1.02, 2.24. High waist circumference (OR = 1.67, CI 95%: 1.16, 2.39, high blood pressure (OR = 0.59, 95% CI: 0.41, 0.85, high triglyceride (OR = 1.85, 95% CI: 1.30, 2.65 and being homozygous for the minor allele of SRB1 (OR = 0.11, 95% CI: 0.01, 0.74 were significantly associated with low HDL. Also, the OR of low HDL in phase 2 of study compared to phase 1 was 1.76 (95% CI: 1.32, 2.35. The result of second order transition model was fairly similar to first order. The parameter estimates of serial dependency are markedly significant, pointing clearly to a first and second-order serial dependence (P < .001. Conclusion: Considering the identification of genetic and environmental factors affecting low HDL over time, transition model was used and the most important risk factors were identified.

  15. Gender differences in the association between HDL cholesterol and the progression of diabetic kidney disease in type 2 diabetic patients.

    Science.gov (United States)

    Hanai, Ko; Babazono, Tetsuya; Yoshida, Naoshi; Nyumura, Izumi; Toya, Kiwako; Hayashi, Toshihide; Bouchi, Ryotaro; Tanaka, Nobue; Ishii, Akiko; Iwamoto, Yasuhiko

    2012-03-01

    The impact of serum lipid abnormalities on the progression of diabetic kidney disease (DKD) remains conflicting. Furthermore, gender differences in the association between dyslipidaemia and outcome of DKD are largely unknown. We therefore conducted this single-centre observational cohort study to clarify gender differences in the association between serum lipid profiles and the progression of DKD. Seven hundred and twenty-three Japanese type 2 diabetes mellitus (T2DM) patients with normoalbuminuria or microalbuminuria, 280 women and 443 men, with a mean (± SD) age of 63 ± 11 years were studied. The endpoint was the progression to a more advanced stage of albuminuria. For statistical analyses, Cox proportional hazard model analyses were conducted. During the mean follow-up period of 4.3 years, 62 of 477 patients with normoalbuminuria and 69 of 246 patients with microalbuminuria reached the endpoint. A significant interaction between high-density lipoprotein (HDL) cholesterol and gender was detected (P(interaction) = 0.04); therefore, separate analyses were conducted for men and women. Overall, in men, the univariate Cox proportional hazard model revealed that higher triglycerides and lower HDL cholesterol levels were significantly associated with higher risk of reaching the endpoint. In the multivariate Cox proportional hazard model, only HDL cholesterol levels remained as an independent predictor of the endpoint (hazard ratio 0.391, P = 0.01). In women, no serum lipid parameters were associated with the endpoint. Lower HDL cholesterol levels seem to be associated with the progression of DKD in men but not in women.

  16. HDL Cholesterol Efflux Capacity: Cardiovascular Risk Factor and Potential Therapeutic Target.

    Science.gov (United States)

    Bhatt, Anish; Rohatgi, Anand

    2016-01-01

    Low high-density lipoprotein cholesterol (HDL-C) levels are associated with incident cardiovascular events; however, many therapies targeting increases in HDL-C have failed to show consistent clinical benefit. Thus, focus has recently shifted toward measuring high-density lipoprotein (HDL) function. HDL is the key mediator of reverse cholesterol transport, the process of cholesterol extraction from foam cells, and eventual excretion into the biliary system. Cholesterol efflux from peripheral macrophages to HDL particles has been associated with atherosclerosis in both animals and humans. We review the mechanism of cholesterol efflux and the emerging evidence on the association between cholesterol efflux capacity and cardiovascular disease in human studies. We also focus on the completed and ongoing trials of novel therapies targeting different aspects of HDL cholesterol efflux.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  19. Diabetic HDL is dysfunctional in stimulating endothelial cell migration and proliferation due to down regulation of SR-BI expression.

    Science.gov (United States)

    Pan, Bing; Ma, Yijing; Ren, Hui; He, Yubin; Wang, Yongyu; Lv, Xiaofeng; Liu, Donghui; Ji, Liang; Yu, Baoqi; Wang, Yuhui; Chen, Y Eugene; Pennathur, Subramaniam; Smith, Jonathan D; Liu, George; Zheng, Lemin

    2012-01-01

    Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (-/-) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (-/-) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically. Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL's capacity to activate Akt chronically.

  20. LDL and HDL transfer rates across peripheral microvascular endothelium agree with those predicted for passive ultrafiltration in humans.

    Science.gov (United States)

    Michel, C Charles; Nanjee, M Nazeem; Olszewski, Waldemar L; Miller, Norman E

    2015-01-01

    The mechanisms by which LDLs and HDLs cross the vascular endothelium from plasma into interstitial fluid are not understood, and have never been studied in humans in vivo. We determined whether the plasma-to-lymph clearance rates of LDL and HDL conform with those predicted by passive ultrafiltration through intercellular pores, or if it is necessary to invoke an active process such as receptor-mediated transcytosis. Plasma and afferent peripheral lymph were collected under steady-state conditions from 30 healthy men, and assayed for seven globular proteins of molecular radii 2.89-8.95 nm, complement C3, and apo AI, apo AII, and apo B. Plasma-to-lymph clearance rates of the seven proteins fitted the relation expected for molecules of their size when transported through two populations of pores of radius 4.95 and 20.1 nm. The same model parameters were then found to accurately predict the clearance rates of both HDL and LDL. The apparent clearance of complement C3, previously shown to be secreted by cultured endothelium, exceeded that predicted by the model. We conclude that the transport of HDL and LDL from plasma into interstitial fluid across the peripheral vascular endothelium in healthy humans can be explained by ultrafiltration without invoking an additional active process such as transcytosis.

  1. Does Ethicality Wane with Adulthood? A Study of the Ethical Values of Entrepreneurship Students and Nascent Entrepreneurs

    Science.gov (United States)

    Lourenço, Fernando; Sappleton, Natalie; Cheng, Ranis

    2015-01-01

    The authors examined the following questions: Does gender influence the ethicality of enterprise students to a greater extent than it does nascent entrepreneurs? If this is the case, then is it due to factors associated with adulthood such as age, work experience, marital status, and parental status? Sex-role socialization theory and moral…

  2. Does Ethicality Wane with Adulthood? A Study of the Ethical Values of Entrepreneurship Students and Nascent Entrepreneurs

    Science.gov (United States)

    Lourenço, Fernando; Sappleton, Natalie; Cheng, Ranis

    2015-01-01

    The authors examined the following questions: Does gender influence the ethicality of enterprise students to a greater extent than it does nascent entrepreneurs? If this is the case, then is it due to factors associated with adulthood such as age, work experience, marital status, and parental status? Sex-role socialization theory and moral…

  3. Advances in the Study of the Antiatherogenic Function and Novel Therapies for HDL

    Directory of Open Access Journals (Sweden)

    Peiqiu Cao

    2015-07-01

    Full Text Available The hypothesis that raising high-density lipoprotein cholesterol (HDL-C levels could improve the risk for cardiovascular disease (CVD is facing challenges. There is multitudinous clear clinical evidence that the latest failures of HDL-C-raising drugs show no clear association with risks for CVD. At the genetic level, recent research indicates that steady-state HDL-C concentrations may provide limited information regarding the potential antiatherogenic functions of HDL. It is evident that the newer strategies may replace therapeutic approaches to simply raise plasma HDL-C levels. There is an urgent need to identify an efficient biomarker that accurately predicts the increased risk of atherosclerosis (AS in patients and that may be used for exploring newer therapeutic targets. Studies from recent decades show that the composition, structure and function of circulating HDL are closely associated with high cardiovascular risk. A vast amount of data demonstrates that the most important mechanism through which HDL antagonizes AS involves the reverse cholesterol transport (RCT process. Clinical trials of drugs that specifically target HDL have so far proven disappointing, so it is necessary to carry out review on the HDL therapeutics.

  4. Research of correlation between LDL-C/HDL-C and TG/HDL-C ratio and severity of coronary heart disease%LDL-C/HDL-C及TG/HDL-C比值与冠状动脉病变程度的相关性研究

    Institute of Scientific and Technical Information of China (English)

    丁超; 小平; 李荣成

    2015-01-01

    目的:探讨LDL-C/HDL-C及TG/HDL-C比值与冠心病病变程度之间的相关性。方法分析169例冠脉造影检查确诊的冠心病患者( CHD组)及103例冠脉造影结果阴性者(对照组) LDL-C/HDL-C及TG/HDL-C比值与冠心病及其病变程度的关系。结果冠心病组患者LDL-C/HDL-C比值及TG/HDL-C比值水平及异常率均明显高于对照组,相关分析显示:LDL-C/HDL-C及TG/HDL-C比值与冠心病及其病变程度均呈正相关,而前者预测意义更大。结论 LDL-C/HDL-C及TG/HDL-C比值可作为预测CHD的指标,且LDL-C/HDL-C比值水平与CHD相关性更强。%Objective To explore the correlation between LDL-C/HDL-C and TG/HDL-C ratio and severity of coronary heart dis-ease.Methods LDL-C/HDL-C and TG/HDL-C ratio was analysed in 272 geriatric cases that underwent coronary angiography, who were positive in 169 geriatric patients(CHD group),and negative in 103 cases(normal control group).Results Both LDL-C/HDL-C and TG/HDL-C ratio and its abnormal rate were significantly higher in patients with CHD than those in the normal control group(P<0.05).Correla-tion analysis and multivariate regression analysis revealed that the ratio had significant positive correlation with coronary heart disease and its severity.Conclusion LDL-C/HDL-C and TG/HDL-C ratio is a good predictive index for CHD.Compared to TG/HDL-C ratio,LDL-C/HDL-C ratio reveals stronger correlation with CHD.

  5. 6-mo aerobic exercise intervention enhances the lipid peroxide transport function of HDL.

    Science.gov (United States)

    Tiainen, Sanna; Luoto, Riitta; Ahotupa, Markku; Raitanen, Jani; Vasankari, Tommi

    2016-01-01

    During acute exercise, the concentration of oxidized high-density lipoprotein (HDL) lipids (ox-HDL) is reported to increase suggesting that HDL may function in decreasing the concentration of oxidized low-density lipoprotein (LDL) lipids. However, the effect of exercise intervention on the lipid peroxide transport function of HDL is unknown. A randomized controlled trial with sedentary women (N = 161), aged 43-63, with no current use of hormone therapy, were randomized into a 6-month (mo) exercise group and a control group. During the 6-mo intervention, the concentration of ox-HDL increased in the exercise group by 5% and decreased in the control group by 2% (p = .003). Also, the ratio of ox-HDL to HDL-cholesterol increased by 5% in the exercise group and decreased by 1.5% in the control group (p = .036). The concentrations of cholesteryl ester transfer protein (CETP) and adiponectin did not change during the intervention. The concentration of serum triglycerides trended to decrease by 6% in the intervention group (p = .051). We found that the concentration of ox-HDL increased during the 6-mo aerobic exercise intervention, but the increase was not related to changes in the levels of CETP or adiponectin. These results, together with earlier studies, suggest that HDL has an active role in the reverse transport of lipid peroxides.

  6. Genetic variation in ABC transporter A1 contributes to HDL cholesterol in the general population

    DEFF Research Database (Denmark)

    Frikke-Schmidt, Ruth; Nordestgaard, Børge G; Jensen, Gorm B

    2004-01-01

    Homozygosity for mutations in ABC transporter A1 (ABCA1) causes Tangier disease, a rare HDL-deficiency syndrome. Whether heterozygosity for genetic variation in ABCA1 also contributes to HDL cholesterol (HDL-C) levels in the general population is presently unclear. We determined whether mutations...... or single-nucleotide polymorphisms (SNPs) in ABCA1 were overrepresented in individuals with the lowest 1% (n=95) or highest 1% (n=95) HDL-C levels in the general population by screening the core promoter and coding region of ABCA1. For all nonsynonymous SNPs identified, we determined the effect of genotype...

  7. High incidence of reduced plasma HDL cholesterol in diabetic patients treated with rosiglitazone and fibrate.

    Science.gov (United States)

    Keidar, Shlomo; Guttmann, Hadassa; Stam, Tamar; Fishman, Ilana; Shapira, Chen

    2007-11-01

    A paradoxical plasma HDL-Cholesterol (HDL-C) reducing effect following combined fibrate and thiazolidinediones (TZDs) therapy was recently reported in occasional cases. As HDL-C level is inversely related to cardiovascular disease (CVD) risk, we have studied the incidence of reduced HDL-C level following mono- and combined therapy with these drugs in a large diabetic population. This study was designed as a retrospective 5-year study. Lipid profile records of 54 000 diabetic patients were searched for transient reduction of HDL-C to levels lower than 17 mg/dL, which was correlated with fibrates and/or TZD treatment. Transient reduction in plasma HDL-C to values lower than 17 mg/dL was observed in 0.02% (2/11 175) of the patients treated with fibrates alone, none of the rosiglitazone-treated patients (0/3213) and in 1.39% (9/649) of patients treated with combination of fibrate and TZD. HDL-C lowering effect was reversible upon stopping either fibrate or rosiglitazone and in some patients it occurred within 2 weeks. In two of the patients, the effect was dose-dependent. Severe reduction in plasma HDL-C is not rare when TZD and fibrates are co-administrated to diabetic hyperlipidemic patients. As low plasma HDL cholesterol is a risk factor for CVD, the physician should be alert to this phenomenon.

  8. HDL lipid composition is profoundly altered in patients with type 2 diabetes and atherosclerotic vascular disease.

    Science.gov (United States)

    Morgantini, C; Meriwether, D; Baldi, S; Venturi, E; Pinnola, S; Wagner, A C; Fogelman, A M; Ferrannini, E; Natali, A; Reddy, S T

    2014-06-01

    We have previously shown that the anti-inflammatory and anti-oxidant functions of HDL are impaired in T2D patients. In this study, we examined whether HDL from T2D patients contains elevated levels of oxidized fatty acids and whether those levels correlate with cardiovascular disease (CVD). HETEs and HODEs on HDL were determined by LC-MS/MS in 40 non-diabetic controls (ND), 40 T2D without CVD (D⁺CVD⁻) and 38 T2D with known history of CVD (D⁺CVD⁺). HDL oxidant index was evaluated by a cell-free assay using dichlorofluorescein. Twenty-six randomly selected subjects from the three groups underwent coronary calcium score evaluation (CAC). Major cardiovascular risk factors were similar among the groups. HETEs and HODEs content were significantly increased in HDL from D⁺CVD⁺ when compared to D⁺CVD⁻ and ND patients. HDL oxidant index was not different among the three groups; however, it was significantly higher in patients with CAC score >100 when compared to patients with CAC score HDL. In the present study, a loss of HDL function (as estimated by the HDL oxidant index) is observed only in patients with more advanced atherosclerosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Apolipoprotein M predicts pre-beta-HDL formation: studies in type 2 diabetic and nondiabetic subjects.

    Science.gov (United States)

    Plomgaard, P; Dullaart, R P F; de Vries, R; Groen, A K; Dahlbäck, B; Nielsen, L B

    2009-09-01

    Studies in mice suggest that plasma apoM is lowered in hyperinsulinaemic diabetes and that apoM stimulates formation of pre-beta-HDL. Pre-beta-HDL is an acceptor of cellular cholesterol and may be critical for reverse cholesterol transport. Herein, we examined whether patients with type 2 diabetes have reduced plasma apoM and whether apoM is associated with pre-beta-HDL formation and cellular cholesterol efflux. In 78 patients with type 2 diabetes and 89 control subjects, we measured plasma apoM with ELISA, pre-beta-HDL and pre-beta-HDL formation, phospholipid transfer protein (PLTP) activity and the ability of plasma to promote cholesterol efflux from cultured fibroblasts. ApoM was approximately 9% lower in patients with type 2 diabetes compared to controls (0.025 +/- 0.006 vs. 0.027 +/- 0.007 g L(-1), P = 0.01). The difference in apoM was largely attributable to diabetes-associated obesity. ApoM was positively related to both HDL (r = 0.16; P = 0.04) and LDL cholesterol (r = 0.28; P = 0.0003). Pre-beta-HDL and pre-beta-HDL formation were not different between diabetic and control subjects. ApoM predicted pre-beta-HDL (r = 0.16; P = 0.04) and pre-beta-HDL formation (r = 0.19; P = 0.02), even independently of positive relationships with apoA-I, HDL-cholesterol and PLTP activity. Cellular cholesterol efflux to plasma was positively related to pre-beta-HDL and PLTP activity but not significantly to apoM. Plasma apoM is modestly reduced in type 2 diabetes. Pre-beta-HDL and pre-beta-HDL formation are positively associated with apoM, supporting the hypothesis that apoM plays a role in HDL remodelling in humans. Lower apoM may provide a mechanism to explain why pre-beta-HDL formation is not increased in type 2 diabetes despite elevated PLTP activity.

  10. Predictors of Impaired HDL Function in HIV-1 Infected Compared to Uninfected Individuals.

    Science.gov (United States)

    Kelesidis, Theodoros; Oda, Michael N; Borja, Mark S; Yee, Yumin; Ng, Kit F; Huynh, Diana; Elashoff, David; Currier, Judith S

    2017-07-01

    High-density lipoprotein (HDL) function rather than absolute level may be a more accurate indicator for cardiovascular disease (CVD). Novel methods can measure HDL function using patient samples. The objective of this study is to identify factors that may contribute to HDL dysfunction in chronic treated HIV-1 infection. Retrospective study of HDL function measured in 2 ways in HIV-1-infected men with low overall CVD risk and healthy men with no known CVD risk matched by race to the HIV-1-infected participants. We examined patient-level factors associated with 2 different measures of HDL dysfunction: reduced antioxidant function (oxidized HDL, HDLox) and reduced HDL-apoA-I exchange (HAE), a measure of HDL remodeling, in the HIV infected and control men. Multivariable-adjusted linear regression analyses were used adjusting for false discovery rate, age, race, body mass index (BMI), CD4 count, viremia, CVD risk, smoking, lipids, apoA-I, and albumin. In multivariate analysis among HIV-1-infected men (n = 166) (median age 45 years, CD4 T-cell count 505 cells/mm, 30.1% were viremic), higher BMI, lower apoA-I, and lower albumin were among the most notable correlates of higher HDLox and lower HAE (P HDL dysfunction in chronic HIV-1 infection using 2 independent methods.

  11. Inflammatory remodeling of the HDL proteome impairs cholesterol efflux capacity[S

    Science.gov (United States)

    Vaisar, Tomáš; Tang, Chongren; Babenko, Ilona; Hutchins, Patrick; Wimberger, Jake; Suffredini, Anthony F.; Heinecke, Jay W.

    2015-01-01

    Recent studies demonstrate that HDL’s ability to promote cholesterol efflux from macrophages associates strongly with cardioprotection in humans independently of HDL-cholesterol (HDL-C) and apoA-I, HDL’s major protein. However, the mechanisms that impair cholesterol efflux capacity during vascular disease are unclear. Inflammation, a well-established risk factor for cardiovascular disease, has been shown to impair HDL’s cholesterol efflux capacity. We therefore tested the hypothesis that HDL’s impaired efflux capacity is mediated by specific changes of its protein cargo. Humans with acute inflammation induced by low-level endotoxin had unchanged HDL-C levels, but their HDL-C efflux capacity was significantly impaired. Proteomic analyses demonstrated that HDL’s cholesterol efflux capacity correlated inversely with HDL content of serum amyloid A (SAA)1 and SAA2. In mice, acute inflammation caused a marked impairment of HDL-C efflux capacity that correlated with a large increase in HDL SAA. In striking contrast, the efflux capacity of mouse inflammatory HDL was preserved with genetic ablation of SAA1 and SAA2. Our observations indicate that the inflammatory impairment of HDL-C efflux capacity is due in part to SAA-mediated remodeling of HDL’s protein cargo. PMID:25995210

  12. Advances in the Study of the Antiatherogenic Function and Novel Therapies for HDL

    Science.gov (United States)

    Cao, Peiqiu; Pan, Haitao; Xiao, Tiancun; Zhou, Ting; Guo, Jiao; Su, Zhengquan

    2015-01-01

    The hypothesis that raising high-density lipoprotein cholesterol (HDL-C) levels could improve the risk for cardiovascular disease (CVD) is facing challenges. There is multitudinous clear clinical evidence that the latest failures of HDL-C-raising drugs show no clear association with risks for CVD. At the genetic level, recent research indicates that steady-state HDL-C concentrations may provide limited information regarding the potential antiatherogenic functions of HDL. It is evident that the newer strategies may replace therapeutic approaches to simply raise plasma HDL-C levels. There is an urgent need to identify an efficient biomarker that accurately predicts the increased risk of atherosclerosis (AS) in patients and that may be used for exploring newer therapeutic targets. Studies from recent decades show that the composition, structure and function of circulating HDL are closely associated with high cardiovascular risk. A vast amount of data demonstrates that the most important mechanism through which HDL antagonizes AS involves the reverse cholesterol transport (RCT) process. Clinical trials of drugs that specifically target HDL have so far proven disappointing, so it is necessary to carry out review on the HDL therapeutics. PMID:26225968

  13. HDL/LDL ratio: a useful parameter for separation of pleural transudates from exudates.

    Science.gov (United States)

    Köktürk, Oğuz; Ulukavak Ciftci, Tansu; Firat, Hikmet; Firat, Serap

    2005-01-01

    The first diagnostic step in pleural effusions is the separation of transudates from exudates. We aimed in present study to investigate the value of HDL/LDL ratio for distinguishing between pleural exudates and transudates. Pleural fluids (PF)from 121 patients, including 28 transudates and 93 exudates were analyzed. The levels of cholesterol, HDL cholesterol and LDL cholesterol in PF were measured. The HDL/LDL ratio was calculated. HDL/LDL ratio found significantly higher in transudates than exudates (p= 0.001). Receiver operating characteristic (ROC) curves were generated and the cut off points determined to the highest level of accuracy and precision. The HDL/LDL ratio was to maximize sensitivity over specificity in the diagnosis of a transudative effusion. The usefulness of HDL/LDL ratio for identifying transudates was evaluated in terms of sensitivity and specificity. The value of pleural HDL/LDL ratio that best differentiated between transudates and exudates was 0.6 (sensitivity 89%, and specificity of 79%). Measurement of HDL and LDL in PF and calculating of HDL/LDL ratio can be proposed to aid for differentiation between pleural exudates and transudates with advantage of not requiring serum levels.

  14. Rare variant in scavenger receptor BI raises HDL cholesterol and increases risk of coronary heart disease

    Science.gov (United States)

    Zanoni, Paolo; Khetarpal, Sumeet A.; Larach, Daniel B.; Hancock-Cerutti, William F.; Millar, John S.; Cuchel, Marina; DerOhannessian, Stephanie; Kontush, Anatol; Surendran, Praveen; Saleheen, Danish; Trompet, Stella; Jukema, J. Wouter; De Craen, Anton; Deloukas, Panos; Sattar, Naveed; Ford, Ian; Packard, Chris; Majumder, Abdullah al Shafi; Alam, Dewan S.; Di Angelantonio, Emanuele; Abecasis, Goncalo; Chowdhury, Rajiv; Erdmann, Jeanette; Nordestgaard, Børge G.; Nielsen, Sune F.; Tybjærg-Hansen, Anne; Schmidt, Ruth Frikke; Kuulasmaa, Kari; Liu, Dajiang J.; Perola, Markus; Blankenberg, Stefan; Salomaa, Veikko; Männistö, Satu; Amouyel, Philippe; Arveiler, Dominique; Ferrieres, Jean; Müller-Nurasyid, Martina; Ferrario, Marco; Kee, Frank; Willer, Cristen J.; Samani, Nilesh; Schunkert, Heribert; Butterworth, Adam S.; Howson, Joanna M. M.; Peloso, Gina M.; Stitziel, Nathan O.; Danesh, John; Kathiresan, Sekar; Rader, Daniel J.

    2016-01-01

    Scavenger receptor BI (SR-BI) is the major receptor for high-density lipoprotein (HDL) cholesterol (HDL-C). In humans, high amounts of HDL-C in plasma are associated with a lower risk of coronary heart disease (CHD). Mice that have depleted Scarb1 (SR-BI knockout mice) have markedly elevated HDL-C levels but, paradoxically, increased atherosclerosis. The impact of SR-BI on HDL metabolism and CHD risk in humans remains unclear. Through targeted sequencing of coding regions of lipid-modifying genes in 328 individuals with extremely high plasma HDL-C levels, we identified a homozygote for a loss-of-function variant, in which leucine replaces proline 376 (P376L), in SCARB1, the gene encoding SR-BI. The P376L variant impairs posttranslational processing of SR-BI and abrogates selective HDL cholesterol uptake in transfected cells, in hepatocyte-like cells derived from induced pluripotent stem cells from the homozygous subject, and in mice. Large population-based studies revealed that subjects who are heterozygous carriers of the P376L variant have significantly increased levels of plasma HDL-C. P376L carriers have a profound HDL-related phenotype and an increased risk of CHD (odds ratio = 1.79, which is statistically significant). PMID:26965621

  15. Automatic Circuit Extractor for HDL Description Using Program Slicing

    Institute of Scientific and Technical Information of China (English)

    Tun Li; Yang Guo; Si-Kun Li

    2004-01-01

    Design extraction and reduction have been extensively used in modern VLSI design process. The extracted and reduced design can be efficiently processed by various applications, such as formal verification,simulation, automatic test pattern generation (ATPG), etc. This paper presents a new circuit extraction method using program slicing technique, and develops an elegant theoretical basis based on program slicing for circuit extraction from Verilog description. The technique can obtain a chaining slice for given signals of interest. Compared with related researches, the main advantages of the method include that it is fine grain; it has no hardware description language (HDL) coding style limitation; it is precise and is capable of dealing with various Verilog constructions. The technique has been integrated with a commercial simulation environment and incorporated into a design process. The results of practical designs show the significant benefits of the approach.

  16. A strategy for co-translational folding studies of ribosome-bound nascent chain complexes using NMR spectroscopy.

    Science.gov (United States)

    Cassaignau, Anaïs M E; Launay, Hélène M M; Karyadi, Maria-Evangelia; Wang, Xiaolin; Waudby, Christopher A; Deckert, Annika; Robertson, Amy L; Christodoulou, John; Cabrita, Lisa D

    2016-08-01

    During biosynthesis on the ribosome, an elongating nascent polypeptide chain can begin to fold, in a process that is central to all living systems. Detailed structural studies of co-translational protein folding are now beginning to emerge; such studies were previously limited, at least in part, by the inherently dynamic nature of emerging nascent chains, which precluded most structural techniques. NMR spectroscopy is able to provide atomic-resolution information for ribosome-nascent chain complexes (RNCs), but it requires large quantities (≥10 mg) of homogeneous, isotopically labeled RNCs. Further challenges include limited sample working concentration and stability of the RNC sample (which contribute to weak NMR signals) and resonance broadening caused by attachment to the large (2.4-MDa) ribosomal complex. Here, we present a strategy to generate isotopically labeled RNCs in Escherichia coli that are suitable for NMR studies. Uniform translational arrest of the nascent chains is achieved using a stalling motif, and isotopically labeled RNCs are produced at high yield using high-cell-density E. coli growth conditions. Homogeneous RNCs are isolated by combining metal affinity chromatography (to isolate ribosome-bound species) with sucrose density centrifugation (to recover intact 70S monosomes). Sensitivity-optimized NMR spectroscopy is then applied to the RNCs, combined with a suite of parallel NMR and biochemical analyses to cross-validate their integrity, including RNC-optimized NMR diffusion measurements to report on ribosome attachment in situ. Comparative NMR studies of RNCs with the analogous isolated proteins permit a high-resolution description of the structure and dynamics of a nascent chain during its progressive biosynthesis on the ribosome.

  17. Patient-Level Discordance in Population Percentiles of the TC/HDL-C Ratio Compared with LDL-C and Non-HDL-C: The Very Large Database of Lipids Study (VLDL-2B)

    Science.gov (United States)

    Elshazly, Mohamed B.; Quispe, Renato; Michos, Erin D.; Sniderman, Allan D.; Toth, Peter P.; Banach, Maciej; Kulkarni, Krishnaji R.; Coresh, Josef; Blumenthal, Roger S.; Jones, Steven R.; Martin, Seth S.

    2015-01-01

    Background The total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C) ratio, estimated low-density lipoprotein cholesterol (LDL-C), and non-HDL-C are routinely available from the standard lipid profile. We aimed to assess the extent of patient-level discordance of TC/HDL-C with LDL-C and non-HDL-C because discordance suggests the possibility of additional information. Methods and Results We compared population percentiles of TC/HDL-C, Friedewald-estimated LDL-C, and non-HDL-C in 1,310,432 U.S. adults from the Very Large Database of Lipids. Lipid testing was performed by ultracentrifugation (VAP, Atherotech, AL). One in three patients had ≥25 percentile units discordance between TC/HDL-C and LDL-C while one in four had ≥25 percentile units discordance between TC/HDL-C and non-HDL-C. The proportion of patients with TC/HDL-C > LDL-C by ≥25 percentile units increased from 3% at triglycerides HDL-C > non-HDL-C discordance by ≥25 percentile units increased from 6% to 21%. In those with HDL-C (HDL-C of 2.6. Age, sex, and directly measured components of the standard lipid profile explained >86% of the variance in percentile discordance between TC/HDL-C vs. LDL-C and non-HDL-C. Conclusions In this contemporary, cross-sectional, big data analysis of U.S. adults who underwent advanced lipid testing, the extent of patient-level discordance suggests that TC/HDL-C may offer potential additional information to LDL-C and non-HDL-C. Future studies are required to determine the clinical implications of this observation. Clinical Trial Registration Information www.clinicaltrials.gov. Identifier: NCT01698489. PMID:26137953

  18. F2-Isoprostanes in HDL are bound to neutral lipids and phospholipids.

    Science.gov (United States)

    Proudfoot, Julie M; Barden, Anne E; Croft, Kevin D; Galano, Jean-Marie; Durand, Thierry; Bultel-Poncé, Valérie; Giera, Martin; Mori, Trevor A

    2016-12-01

    Low HDL cholesterol (HDL-C) is a risk factor for coronary artery disease (CAD). However, interventions that raise HDL-C have failed to reduce cardiovascular events. We previously reported that HDL is the main carrier of plasma F2-isoprostanes (F2-IsoPs) that are markers of oxidative stress formed upon oxidation of arachidonic acid. F2-IsoPs are predominantly associated with phospholipids. However, there is evidence that F2-IsoPs in the liver of rats treated with carbon tetrachloride associate with the neutral lipids. To date it is not known whether F2-IsoPs are found in the neutral lipids in HDL in humans. Possible candidate neutral lipids include cholesteryl esters, triglycerides, diglycerides, and monoglycerides. This study aimed to identify the lipid classes within native and oxidized HDL that contain F2-IsoPs. We showed that F2-IsoPs in HDL are bound to neutral lipids as well as phospholipids. HDL-3 contained the highest concentration of F2-IsoPs in all lipid classes before and after in vitro oxidation. Using targeted LC/MS and high resolution MS, we were unable to provide conclusive evidence for the presence of the synthesized standards 15(R)-15-F2t-isoP cholesterol and 1-ent-15(RS)-15-F2t-isoprostanoyl-sn-glycerol in the neutral lipids of HDL. Our findings show that oxidized lipids such as F2-IsoPs are found in the core and surface of HDL. However, the exact molecular species remain to be definitively characterized. Future studies are required to determine whether the presence of F2-IsoPs in neutral lipids alters HDL function.

  19. Effects of modified LDL and HDL on retinal pigment epithelial cells: a role in diabetic retinopathy?

    Science.gov (United States)

    Du, M; Wu, M; Fu, D; Yang, S; Chen, J; Wilson, K; Lyons, T J

    2013-10-01

    Blood-retina barrier leakage in diabetes results in extravasation of plasma lipoproteins. Intra-retinal modified LDLs have been implicated in diabetic retinopathy (DR), but their effects on retinal pigment epithelial (RPE) cells and the added effects of extravasated modified HDLs are unknown. In human retinas from individuals with and without diabetes and DR, immunohistochemistry was used to detect ApoB, ApoA1 and endoplasmic reticulum (ER) stress markers. In cell culture, human RPE cells were treated with native LDL (N-LDL) or heavily-oxidised glycated LDL (HOG-LDL) with or without pretreatment with native HDL (N-HDL) or heavily-oxidised glycated HDL (HOG-HDL). Cell viability, oxidative stress, ER stress, apoptosis and autophagy were assessed by Cell Counting Kit-8 assay, dichlorofluorescein assay, western blotting, immunofluorescence and TUNEL assay. In separate experiments, RPE cells were treated with lipid oxidation products, 7-ketocholesterol (7-KC, 5-40 μmol/l) or 4-hydroxynonenal (4-HNE, 5-80 μmol/l), with or without pretreatment with N-HDL or HOG-HDL. ApoB, ApoA1 staining and RPE ER stress were increased in the presence of DR. HOG-LDL but not N-LDL significantly decreased RPE cell viability and increased reactive oxygen species generation, ER stress, apoptosis and autophagy. Similarly, 4-HNE and 7-KC decreased viability and induced ER stress. Pretreatment with N-HDL mitigated these effects, whereas HOG-HDL was less effective by most, but not all, measures. In DR, extravascular modified LDL may promote RPE injury through oxidative stress, ER stress, autophagy and apoptosis. N-HDL has protective effects, but HOG-HDL is less effective. Extravasation and modification of HDL may modulate the injurious effects of extravasated modified LDL on the retinal pigment epithelium.

  20. Xanthophylls, phytosterols and pre-β1-HDL are differentially affected by fenofibrate and niacin HDL-raising in a cross-over study.

    Science.gov (United States)

    Niesor, Eric J; Gauthamadasa, Kekulawalage; Silva, R A Gangani D; Suchankova, Gabriela; Kallend, David; Gylling, Helena; Asztalos, Bela; Damonte, Elisabetta; Rossomanno, Simona; Abt, Markus; Davidson, W Sean; Benghozi, Renee

    2013-12-01

    Fenofibrate and extended-release (ER) niacin similarly raise high-density lipoprotein cholesterol (HDL-C) concentration but their effects on levels of potent plasma antioxidant xanthophylls (lutein and zeaxanthin) and phytosterols obtained from dietary sources, and any relationship with plasma lipoproteins and pre-β1-HDL levels, have not been investigated. We studied these parameters in 66 dyslipidemic patients treated for 6 week with fenofibrate (160 mg/day) or ER-niacin (0.5 g/day for 3 week, then 1 g/day) in a cross-over study. Both treatments increased HDL-C (16 %) and apolipoprotein (apo) A-I (7 %) but only fenofibrate increased apoA-II (28 %). Lutein and zeaxanthin levels were unaffected by fenofibrate but inversely correlated with percentage change in apoB and low-density lipoprotein cholesterol and positively correlated with end of treatment apoA-II. ApoA-II in isolated HDL in vitro bound more lutein than apoA-I. Xanthophylls were increased by ER-niacin (each ~30 %) without any correlation to lipoprotein or apo levels. Only fenofibrate markedly decreased plasma markers of cholesterol absorption; pre-β1-HDL was significantly decreased by fenofibrate (-19 %, p fenofibrate and ER-niacin similarly increased plasma HDL-C and apoA-I, effects on plasma xanthophylls, phytosterols and pre-β1-HDL differed markedly, suggesting differences in intestinal lipidation of HDL. In addition, the in vitro investigations suggest an important role of plasma apoA-II in xanthophyll metabolism.

  1. Lipid transfers to HDL are diminished in long-term bedridden patients: association with low HDL-cholesterol and increased inflammatory markers.

    Science.gov (United States)

    de Oliveira, Wilson Pascoalino Camargo; Tavoni, Thauany Martins; Freitas, Fatima Rodrigues; Silva, Bruna Miranda Oliveira; Maranhão, Raul Cavalcante

    2017-08-01

    Plasma lipids have been extensively studied in sedentary and in subjects practicing exercise training, but not in extreme inactivity as occurs in bedridden patients. This is important for the care of bedridden patients and understanding the overall plasma lipid regulation. Here, we investigated plasma lipids, lipid transfers to HDL and inflammatory markers in bedridden patients. Fasting blood samples were collected from 23 clinically stable bedridden patients under long-term care (>90 days) and 26 normolipidemic sedentary subjects, paired for age and gender. In vitro transfer of four lipids to HDL was performed by incubating plasma with donor nanoparticles containing radioactive lipids. Total (193 ± 36 vs 160 ± 43, p = 0.005), LDL (124 ± 3 vs 96 ± 33 p = 0.003) and HDL-cholesterol (45 ± 10 vs 36 ± 13, p = 0.008), apolipoprotein A-I (134 ± 20 vs 111 ± 24, p = 0.001) and oxidized LDL (53 ± 13 vs 43 ± 12, p = 0.011) were lower in bedridden patients, whereas triglycerides, apolipoprotein B, CETP and LCAT were equal in both groups. Transfers of all lipids, namely unesterified cholesterol, cholesterol esters, triglycerides and phospholipids, to HDL were lower in bedridden patients, probably due to their lower HDL-cholesterol levels. Concentrations of IL-1β, IL-6, IL-8, HGF and NGF were higher in bedridden patients compared to sedentary subjects. In conclusion, inactivity had great impact on HDL, by lowering HDL-cholesterol, apolipoprotein A-I and thereby cholesterol transfers to the lipoprotein, which suggests that inactivity may deteriorate HDL protection beyond the ordinary sedentary condition.

  2. Insulin-induced glucose control improves HDL cholesterol levels but not reverse cholesterol transport in type 2 diabetic patients.

    Science.gov (United States)

    Fadini, Gian Paolo; Iori, Elisabetta; Marescotti, Maria Cristina; Vigili de Kreutzenberg, Saula; Avogaro, Angelo

    2014-08-01

    Type 2 diabetes (T2D) is characterized by low HDL cholesterol (HDL-C) and HDL dysfunction. We herein tested whether lowering HbA1c affects HDL-C and reverse cholesterol transport (RCT). Forty-two uncontrolled T2D patients initiating basal insulin were included. HbA1c, HDL-C and RCT were assessed at baseline and after 6 months. At baseline, HDL-C and RCT were directly correlated (r = 0.50; p HDL-C and RCT did not change. Follow-up HDL-C and RCT were still correlated (r = 0.31; p = 0.033) and ΔHDL-C correlated with ΔRCT (r = 0.32; p = 0.029). ΔHbA1c correlated with ΔHDL-C (r = 0.43, p = 0.001), but not with ΔRCT. In patients with ΔHbA1c above the median value (1.3%), HDL-C (but not RCT) increased significantly. In conclusion, glucose control correlates with increased HDL-C, but not with improved RCT. Thus, persistent HDL dysfunction despite improved HbA1c and HDL-C can contribute to residual cardiovascular risk in T2D. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. A study on a nascent entomopathogenic association between caenorhabditis briggsae and serratia sp.SCBI

    Science.gov (United States)

    Abebe-Akele, Feseha

    Life is inconceivable in the absence of interactions which could be cooperative, antagonistic or neutral. Interactions are in constant flux because on one hand it is often difficult to demarcate where one form of interaction ends and the other begins on the other hand what is cooperative at one point in time could evolve into antagonistic or neutral or vice versa. Thus, organisms, as a consequence of mutation, adaptation and natural selection would inevitably enter into natural associations from which they emerge as mutual partners, inveterate enemies or passive cohabitants. Entomopathogenic nematode (EPN) partnerships are tripartite interactions where a nematode-bacteria symbiont duo attacks a third organism -an insect or insect larva-for the mutual benefit of the attacking partners and the detriment of the insect they invade. All three participants in the interaction---the nematode worms with their symbiont bacteria and the target insect host-are among the most ancient, diverse and abundant species on earth, however, these EPN partnerships are not as common as circumstances would suggest. EPN associations, which are arguably at the peak of evolutionary co adaptations, where two primitive forms of life cooperate to take advantage of a larger species are not only fascinating but immensely important for humans. The biological and molecular mechanisms underlying entomopathogenesis have been studied in great detail for decades for their potential as biological control agents against invasive insects. In spite of intense research in The EPN field, the evolutionary history of EPN associations are largely unknown because there are no known intermediate forms. In this thesis, a nascent EPN partnership is described between Caenorhabditid nematodes and Serratia sp. SCBI. Comparative analysis of this association with other EPNs suggests that crucial aspect of EPN associations may be the ability of partners to co-exist without killing each other and that the end results of

  4. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    de Munter Jeroen SL

    2011-11-01

    Full Text Available Abstract Background Evidence suggests that physical activity (PA has a beneficial effect on high-density lipoprotein cholesterol (HDL and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the PA composition. The aim of this study was to assess the relationship of the total PA, along with its intensity and duration, with HDL and triglycerides in a multi-ethnic population. Methods The study population was sampled from the SUNSET study and included: 502 European- Dutch, 338 Hindustani-Surinamese, and 596 African-Surinamese participants living in Amsterdam, the Netherlands. We assessed PA with the SQUASH questionnaire. We calculated age-sex-adjusted betas, geometric mean ratios (GMRs, and prevalence ratios (PRs to assess the relationship of PA with HDL and triglycerides. Results In the adjusted models, the highest total PA tertile compared to the lowest tertile was beneficially associated with HDL (beta: 0.08, 95% CI: 0.00, 0.16 and PR low HDL 0.59, 95% CI: 0.39, 0.88 and triglycerides (GMR: 0.93, 95% CI: 0.83, 1.03 and PR: 0.56, 95% CI: 0.29, 1.08 for the African-Surinamese. No statistically significant associations appeared for total PA among the European-Dutch and Hindustani-Surinamese. The adjusted models with the intensity score and HDL showed beneficial associations for the European-Dutch (beta: 0.06, 95% CI: 0.03, 0.10 and African-Surinamese (beta: 0.06, 0.02, 0.10, for log triglycerides for the European-Dutch (beta: -0.08, 95% CI: -0.12, 0.03, Hindustani-Surinamese (beta: -0.06, 95% CI: -0.16, 0.03, and African-Surinamese (beta: -0.04, 95% CI: -0.10, 0.01. Excepting HDL in African-Surinamese, the duration score was unrelated to HDL and triglycerides in any group. Conclusions Activity intensity related beneficially to blood lipids in almost every ethnic group. The activity duration was unrelated to blood lipids, while

  5. Knowledge-driven multi-locus analysis reveals gene-gene interactions influencing HDL cholesterol level in two independent EMR-linked biobanks.

    Science.gov (United States)

    Turner, Stephen D; Berg, Richard L; Linneman, James G; Peissig, Peggy L; Crawford, Dana C; Denny, Joshua C; Roden, Dan M; McCarty, Catherine A; Ritchie, Marylyn D; Wilke, Russell A

    2011-05-11

    Genome-wide association studies (GWAS) are routinely being used to examine the genetic contribution to complex human traits, such as high-density lipoprotein cholesterol (HDL-C). Although HDL-C levels are highly heritable (h(2)∼0.7), the genetic determinants identified through GWAS contribute to a small fraction of the variance in this trait. Reasons for this discrepancy may include rare variants, structural variants, gene-environment (GxE) interactions, and gene-gene (GxG) interactions. Clinical practice-based biobanks now allow investigators to address these challenges by conducting GWAS in the context of comprehensive electronic medical records (EMRs). Here we apply an EMR-based phenotyping approach, within the context of routine care, to replicate several known associations between HDL-C and previously characterized genetic variants: CETP (rs3764261, p = 1.22e-25), LIPC (rs11855284, p = 3.92e-14), LPL (rs12678919, p = 1.99e-7), and the APOA1/C3/A4/A5 locus (rs964184, p = 1.06e-5), all adjusted for age, gender, body mass index (BMI), and smoking status. By using a novel approach which censors data based on relevant co-morbidities and lipid modifying medications to construct a more rigorous HDL-C phenotype, we identified an association between HDL-C and TRIB1, a gene which previously resisted identification in studies with larger sample sizes. Through the application of additional analytical strategies incorporating biological knowledge, we further identified 11 significant GxG interaction models in our discovery cohort, 8 of which show evidence of replication in a second biobank cohort. The strongest predictive model included a pairwise interaction between LPL (which modulates the incorporation of triglyceride into HDL) and ABCA1 (which modulates the incorporation of free cholesterol into HDL). These results demonstrate that gene-gene interactions modulate complex human traits, including HDL cholesterol.

  6. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study

    Science.gov (United States)

    2011-01-01

    Background Evidence suggests that physical activity (PA) has a beneficial effect on high-density lipoprotein cholesterol (HDL) and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the PA composition. The aim of this study was to assess the relationship of the total PA, along with its intensity and duration, with HDL and triglycerides in a multi-ethnic population. Methods The study population was sampled from the SUNSET study and included: 502 European- Dutch, 338 Hindustani-Surinamese, and 596 African-Surinamese participants living in Amsterdam, the Netherlands. We assessed PA with the SQUASH questionnaire. We calculated age-sex-adjusted betas, geometric mean ratios (GMRs), and prevalence ratios (PRs) to assess the relationship of PA with HDL and triglycerides. Results In the adjusted models, the highest total PA tertile compared to the lowest tertile was beneficially associated with HDL (beta: 0.08, 95% CI: 0.00, 0.16 and PR low HDL 0.59, 95% CI: 0.39, 0.88) and triglycerides (GMR: 0.93, 95% CI: 0.83, 1.03 and PR: 0.56, 95% CI: 0.29, 1.08) for the African-Surinamese. No statistically significant associations appeared for total PA among the European-Dutch and Hindustani-Surinamese. The adjusted models with the intensity score and HDL showed beneficial associations for the European-Dutch (beta: 0.06, 95% CI: 0.03, 0.10) and African-Surinamese (beta: 0.06, 0.02, 0.10), for log triglycerides for the European-Dutch (beta: -0.08, 95% CI: -0.12, 0.03), Hindustani-Surinamese (beta: -0.06, 95% CI: -0.16, 0.03), and African-Surinamese (beta: -0.04, 95% CI: -0.10, 0.01). Excepting HDL in African-Surinamese, the duration score was unrelated to HDL and triglycerides in any group. Conclusions Activity intensity related beneficially to blood lipids in almost every ethnic group. The activity duration was unrelated to blood lipids, while the total PA

  7. Total physical activity might not be a good measure in the relationship with HDL cholesterol and triglycerides in a multi-ethnic population: a cross-sectional study.

    Science.gov (United States)

    de Munter, Jeroen S L; van Valkengoed, Irene G; Stronks, Karien; Agyemang, Charles

    2011-11-30

    Evidence suggests that physical activity (PA) has a beneficial effect on high-density lipoprotein cholesterol (HDL) and triglycerides. However, observational studies show contrasting results for this association between different ethnic groups. It is unclear whether this is due to differences in the PA composition. The aim of this study was to assess the relationship of the total PA, along with its intensity and duration, with HDL and triglycerides in a multi-ethnic population. The study population was sampled from the SUNSET study and included: 502 European- Dutch, 338 Hindustani-Surinamese, and 596 African-Surinamese participants living in Amsterdam, the Netherlands. We assessed PA with the SQUASH questionnaire. We calculated age-sex-adjusted betas, geometric mean ratios (GMRs), and prevalence ratios (PRs) to assess the relationship of PA with HDL and triglycerides. In the adjusted models, the highest total PA tertile compared to the lowest tertile was beneficially associated with HDL (beta: 0.08, 95% CI: 0.00, 0.16 and PR low HDL 0.59, 95% CI: 0.39, 0.88) and triglycerides (GMR: 0.93, 95% CI: 0.83, 1.03 and PR: 0.56, 95% CI: 0.29, 1.08) for the African-Surinamese. No statistically significant associations appeared for total PA among the European-Dutch and Hindustani-Surinamese. The adjusted models with the intensity score and HDL showed beneficial associations for the European-Dutch (beta: 0.06, 95% CI: 0.03, 0.10) and African-Surinamese (beta: 0.06, 0.02, 0.10), for log triglycerides for the European-Dutch (beta: -0.08, 95% CI: -0.12, 0.03), Hindustani-Surinamese (beta: -0.06, 95% CI: -0.16, 0.03), and African-Surinamese (beta: -0.04, 95% CI: -0.10, 0.01). Excepting HDL in African-Surinamese, the duration score was unrelated to HDL and triglycerides in any group. Activity intensity related beneficially to blood lipids in almost every ethnic group. The activity duration was unrelated to blood lipids, while the total PA 'summary score' was associated only with

  8. Increased oxidative stress in scavenger receptor BI knockout mice with dysfunctional HDL

    NARCIS (Netherlands)

    Van Eck, Miranda; Hoekstra, Menno; Hildebrand, Reeni B.; Yaong, Yuemang; Stengel, Dominique; Kruijt, J. Kar; Sattler, Wolfgang; Tietge, Uwe J. F.; Ninio, Ewa; Van Berkel, Theo J. C.; Pratico, Domenico

    2007-01-01

    Objective-In the current study the effect of disruption of SR-BI, a prominent regulator of HDL metabolism, on the activity of the HDL-associated antioxidant enzymes PON1 and PAF-AH as well as in vivo oxidative stress were investigated. Methods and Results-SR-BI deficiency resulted in 1.4-fold (P

  9. Original Paper Performances comparées du HDL-cholestérol et du ...

    African Journals Online (AJOL)

    CT/HDL-C) et du HDL-Cholestérol est le meilleur prédicteur du SMet chez les adultes béninois. L'étude de ..... d'hypertension artérielle avaient observé qu'une ... facteurs tels que l'alimentation et l'activité physique sur les lipides sanguins.

  10. HDL cholesterol levels are an important factor for determining the lifespan of erythrocytes

    NARCIS (Netherlands)

    Meurs, I.; Hoekstra, M; van Wanrooij, EJA; Hildebrand, RB; Kuiper, J; Kuipers, F; Hardeman, MR; Van Berkel, TJC; Van Eck, M

    2005-01-01

    Objective. Scavenger receptor class B, type I (SR-BI) is a multifunctional receptor that promotes the selective uptake of cholesteryl esters from high-density lipoprotein (HDL). Disruption of SR-BI in mice results in a dramatic increase in HDL cholesterol. Interestingly, mice lacking SR-BI also deve

  11. Increased oxidative stress in scavenger receptor BI knockout mice with dysfunctional HDL

    NARCIS (Netherlands)

    Van Eck, Miranda; Hoekstra, Menno; Hildebrand, Reeni B.; Yaong, Yuemang; Stengel, Dominique; Kruijt, J. Kar; Sattler, Wolfgang; Tietge, Uwe J. F.; Ninio, Ewa; Van Berkel, Theo J. C.; Pratico, Domenico

    2007-01-01

    Objective-In the current study the effect of disruption of SR-BI, a prominent regulator of HDL metabolism, on the activity of the HDL-associated antioxidant enzymes PON1 and PAF-AH as well as in vivo oxidative stress were investigated. Methods and Results-SR-BI deficiency resulted in 1.4-fold (P Con

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

    NARCIS (Netherlands)

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

    2010-01-01

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  13. eNOS Activation by HDL Is Impaired in Genetic CETP Deficiency

    NARCIS (Netherlands)

    Gomaraschi, Monica; Ossoli, Alice; Pozzi, Silvia; Nilsson, Peter; Cefalu, Angelo B.; Averna, Maurizio; Kuivenhoven, Jan Albert; Hovingh, G. Kees; Veglia, Fabrizio; Franceschini, Guido; Calabresi, Laura

    2014-01-01

    Mutations in the CETP gene resulting in defective CETP activity have been shown to cause remarkable elevations of plasma HDL-C levels, with the accumulation in plasma of large, buoyant HDL particles enriched in apolipoprotein E. Genetic CETP deficiency thus represents a unique tool to evaluate how s

  14. Endothelium-protective sphingosine-1-phosphate provided by HDL-associated apolipoprotein M

    DEFF Research Database (Denmark)

    Christoffersen, Christina; Obinata, Hideru; Kumaraswamy, Sunil B

    2011-01-01

    Protection of the endothelium is provided by circulating sphingosine-1-phosphate (S1P), which maintains vascular integrity. We show that HDL-associated S1P is bound specifically to both human and murine apolipoprotein M (apoM). Thus, isolated human ApoM(+) HDL contained S1P, whereas ApoM(-) HDL did...... not. Moreover, HDL in Apom(-/-) mice contains no S1P, whereas HDL in transgenic mice overexpressing human apoM has an increased S1P content. The 1.7-Å structure of the S1P-human apoM complex reveals that S1P interacts specifically with an amphiphilic pocket in the lipocalin fold of apoM. Human ApoM......(+) HDL induced S1P(1) receptor internalization, downstream MAPK and Akt activation, endothelial cell migration, and formation of endothelial adherens junctions, whereas apoM(-) HDL did not. Importantly, lack of S1P in the HDL fraction of Apom(-/-) mice decreased basal endothelial barrier function in lung...

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

    NARCIS (Netherlands)

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

    2011-01-01

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

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

    NARCIS (Netherlands)

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

    There is unequivocal evidence of an inverse association between plasma high-density lipoprotein (HDL) cholesterol concentrations and the risk of cardiovascular disease, a finding that has led to the hypothesis that HDL protects from atherosclerosis. This review details the experimental evidence for

  17. Oxidative stress, HDL functionality and effects of intravenous iron administration in women with iron deficiency anemia.

    Science.gov (United States)

    Meroño, Tomás; Dauteuille, Carolane; Tetzlaff, Walter; Martín, Maximiliano; Botta, Eliana; Lhomme, Marie; Saez, María Soledad; Sorroche, Patricia; Boero, Laura; Arbelbide, Jorge; Chapman, M John; Kontush, Anatol; Brites, Fernando

    2017-04-01

    Iron deficiency anemia (IDA) affects around 20-30% of adults worldwide. An association between IDA and cardiovascular disease (CVD) has been reported. Oxidative stress, inflammation and low concentration of high-density lipoproteins (HDL) were implicated on endothelial dysfunction and CVD in IDA. We studied the effects of iron deficiency and of an intravenous iron administration on oxidative stress and HDL characteristics in IDA women. Two studies in IDA women are presented: a case-control study, including 18 patients and 18 age-matched healthy women, and a follow-up study 72hr after the administration of intravenous iron (n = 16). Lipids, malondialdehyde, cholesteryl ester transfer protein (CETP), paraoxonase-1 (PON-1) and HDL chemical composition and functionality (cholesterol efflux and antioxidative activity) were measured. Cell cholesterol efflux from iron-deficient macrophages to a reference HDL was also evaluated. IDA patients showed higher triglycerides and CETP activity and lower HDL-C than controls (all p HDL particles from IDA patients showed higher triglyceride content (+30%,p HDL-mediated cholesterol efflux was similar between the patients and controls, iron deficiency provoked a significant reduction in macrophage cholesterol efflux (-25%,p HDL particles. It remains to be determined if such alterations suffice to impair endothelial function in IDA. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  18. eNOS Activation by HDL Is Impaired in Genetic CETP Deficiency

    NARCIS (Netherlands)

    Gomaraschi, Monica; Ossoli, Alice; Pozzi, Silvia; Nilsson, Peter; Cefalu, Angelo B.; Averna, Maurizio; Kuivenhoven, Jan Albert; Hovingh, G. Kees; Veglia, Fabrizio; Franceschini, Guido; Calabresi, Laura

    2014-01-01

    Mutations in the CETP gene resulting in defective CETP activity have been shown to cause remarkable elevations of plasma HDL-C levels, with the accumulation in plasma of large, buoyant HDL particles enriched in apolipoprotein E. Genetic CETP deficiency thus represents a unique tool to evaluate how

  19. Trans Fatty Acids, HDL-cholesterol, and Cardiovascular Disease. Effects of Dietary Changes on Vascular Reactivity

    NARCIS (Netherlands)

    Roos, de N.M.; Schouten, E.G.; Katan, M.B.

    2003-01-01

    A high consumption of trans fatty acids increases the risk of cardiovascular disease (CVD). We investigeted whether this increase in risk was due to the decrease in serum HDL-cholesterol by trans fatty acids, because low concentrations of serum HDL-cholesterol also increase risk of CVD. Flow-mediate

  20. The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio as a predictor of β-cell function in African American women.

    Science.gov (United States)

    Maturu, Amita; DeWitt, Peter; Kern, Philip A; Rasouli, Neda

    2015-05-01

    The TG/HDL-C ratio is used as a marker of insulin resistance (IR) in Caucasians. However, there are conflicting data on TG/HDL-C ratio as a predictor of IR in African Americans. Compared to Caucasians, African Americans have lower TG levels and increased insulin levels despite a greater risk for diabetes. We hypothesized that the TG/HDL-C ratio is predictive of IR and/or β-cell function in African American (AA) women. Non-diabetic AA women (n = 41) with a BMI > 25 kg/m(2) underwent frequently sampled intravenous glucose tolerance test (FSIGTT). Insulin sensitivity (SI) and the acute insulin response to glucose (AIRg) were measured using minimal model and β-cell function was determined by disposition index (DI = S I*AIRg). IR was defined as the lowest tertile of SI ( 0.70 was defined as significant discrimination. The mean (± SD) age was 38.5 ± 11.3 years, with BMI of 33.5 ± 6.7 kg/m(2) and fasting glucose of 86.5 ± 10.5 mg/dL. The AUC-ROC for the prediction of DI HDL-C ratio was associated with decreased DI. However, the AUC-ROC for prediction of IR or low AIRg (HDL-C ratio is a poor predictor of IR in AA women. However, we did show an inverse association between the TG/HDL-C ratio and β-cell function, suggesting that this simple tool may effectively identify AA women at risk for DM2. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Temporal Analysis and Automatic Calibration of the Velodyne HDL-32E LiDAR System

    Science.gov (United States)

    Chan, T. O.; Lichti, D. D.; Belton, D.

    2013-10-01

    At the end of the first quarter of 2012, more than 600 Velodyne LiDAR systems had been sold worldwide for various robotic and high-accuracy survey applications. The ultra-compact Velodyne HDL-32E LiDAR has become a predominant sensor for many applications that require lower sensor size/weight and cost. For high accuracy applications, cost-effective calibration methods with minimal manual intervention are always desired by users. However, the calibrations are complicated by the Velodyne LiDAR's narrow vertical field of view and the very highly time-variant nature of its measurements. In the paper, the temporal stability of the HDL-32E is first analysed as the motivation for developing a new, automated calibration method. This is followed by a detailed description of the calibration method that is driven by a novel segmentation method for extracting vertical cylindrical features from the Velodyne point clouds. The proposed segmentation method utilizes the Velodyne point cloud's slice-like nature and first decomposes the point clouds into 2D layers. Then the layers are treated as 2D images and are processed with the Generalized Hough Transform which extracts the points distributed in circular patterns from the point cloud layers. Subsequently, the vertical cylindrical features can be readily extracted from the whole point clouds based on the previously extracted points. The points are passed to the calibration that estimates the cylinder parameters and the LiDAR's additional parameters simultaneously by constraining the segmented points to fit to the cylindrical geometric model in such a way the weighted sum of the adjustment residuals are minimized. The proposed calibration is highly automatic and this allows end users to obtain the time-variant additional parameters instantly and frequently whenever there are vertical cylindrical features presenting in scenes. The methods were verified with two different real datasets, and the results suggest that up to 78

  2. 升高高密度脂蛋白胆固醇(HDL-C)面临的挑战——升HDL-C药物的不同机制和HDL-C升高的疗效评价

    Institute of Scientific and Technical Information of China (English)

    曲鹏; 王虹艳

    2008-01-01

    高密度脂蛋白胆固醇(HDL-C)水平与发生冠心病的危险性呈负相关。HDL通过促进胆固醇逆转运、改善内皮功能、抗氧化、抗炎和抗血栓而发挥心血管保护作用。HDL已成为冠心病防治工作的新靶点,生活方式和调脂药物的干预能升高HDL-C,然而HDL的功能比HDL-C血浆水平更重要,多项以HDL为靶点新的治疗措施正在研究中,临床上如何评价HDL-C升高的疗效价值及升高HDL-C的药物和策略有着重要意义。进一步研究HDL的结构、代谢和功能能够深入了解脂质代谢过程和动脉粥样硬化发生机制,使干预HDL成为动脉粥样硬化防治新的目标。

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

    Science.gov (United States)

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

    2015-11-01

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

  4. Entrepreneurial Judgment and Value Capture, the Case of the Nascent Offshore Renewable Industry

    Directory of Open Access Journals (Sweden)

    Truls Erikson

    2015-11-01

    Full Text Available Entrepreneurship may be regarded as the mechanism of change towards sustainability. Any entrepreneur that seeks to start a new venture in an emerging industry will face resource and time constraints. The question we raise here is how the entrepreneur should prioritize use of time and resources to increase likeliness of success. To address this question we depart from a theoretical perspective of entrepreneurship seen as judgment, and bridges it over to entrepreneurship seen as co-creation. In other words, we combine the subjective with the intersubjective, and explore the effects of the actions successful green technology entrepreneurs in the emerging offshore renewable energy industry make in building their new ventures in nascent markets. Inspired by earlier studies on market entry, combined with new ways to understand new venture emergence, we find that independent entrepreneurs benefit from leapfrogging typical stages in the technology development process and rather devote time and efforts on resource acquisition. We also find that the most important value-capturing, decision-making heuristics are those related to “hybrid governance”. We discuss implications for theory, practice, and policy.

  5. L30 binds the nascent RPL30 transcript to repress U2 snRNP recruitment.

    Science.gov (United States)

    Macías, Sara; Bragulat, Mireia; Tardiff, Daniel F; Vilardell, Josep

    2008-06-20

    The mechanisms of pre-mRNA splicing regulation are poorly understood. Here we dissect how the Saccharomyces cerevisiae ribosomal L30 protein blocks splicing of its pre-mRNA upon binding a kink-turn structure including the 5' splice site. We show that L30 binds the nascent RPL30 transcript without preventing recognition of the 5' splice site by U1 snRNP but blocking U2 snRNP association with the branch site. Interaction of the factors BBP and Mud2 with the intron, relevant for U2 snRNP recruitment, is not affected by L30. Furthermore, the functions of neither the DEAD-box protein Sub2 in the incipient spliceosome nor the U2 snRNP factor Cus2 on branch site recognition are required for L30 inhibition. These findings contrast with the effects caused by binding a heterologous protein to the same region, completely blocking intron recognition. Collectively, our data suggest that L30 represses a spliceosomal rearrangement required for U2 snRNP association with the transcript.

  6. Research document no.31. Integration of European gas markets: nascent competition in a diversity of models

    Energy Technology Data Exchange (ETDEWEB)

    Finon, D

    2002-07-01

    The idea of building an integrated European gas market based on competitive trade, like a gas lake supplied indifferently by remote, intra-European and national sources with the help of active market places allowing arbitration and price convergence, is far from being reached. In fact it depends upon two conditions: the deregulation of each gas market at national level, and at the upper level of the market the change in contractual relations between remote gas producers and buyers, who currently make the relations rigid with long-term transactions and limit opportunities for exchange on a competitive basis. This document analyses at two levels, namely national and European, the changing shape of the European gas markets under the effects of the market reforms and their chance of integration. Firstly the former two-level European gas market, the legacy of which determines the constraints on competition development more strongly than in electricity, are characterized. Secondly, in order to characterize the potential for development of competition, the main traits of each national gas market are identified in terms of market attractiveness and market accessibility for the incumbents competitors. Thirdly, dynamics of market development towards market integration are inferred at European level from these characteristics and from the possibility for development of new forms of gas trade between foreign producers, suppliers and users at national level. (A.L.B.)

  7. A very high prevalence of low HDL cholesterol in Spanish patients with acute coronary syndromes.

    Science.gov (United States)

    Pintó, Xavier; Millán, Jesús; Muñoz, Anna; Corbella, Emili; Hernández-Mijares, Antonio; Zuñiga, Manuel; Mangas, Alipio; Pedro-Botet, Juan

    2010-07-01

    Total and low-density lipoprotein cholesterol (LDL-C) concentrations in coronary artery disease have progressively declined, although high-density lipoprotein cholesterol (HDL-C) has not always been evaluated. The prevalence and related factors of low HDL-C in a cohort of Spanish patients with acute coronary syndromes (ACS) were assessed. Clinical and laboratory data registered at admission and at discharge of 648 patients admitted to coronary care units of 6 Spanish hospitals for ACS between January 2004 and September 2007 were analyzed. Low HDL-C (HDL-C < 1.04 mmol/L) was observed in 367 (56.6%) patients. Male gender, smoking, hypertension, diabetes, high body mass index, and triglycerides were related to low HDL-C. Female gender was the strongest protective factor against low HDL-C (0.619; 95% confidence interval [CI]: 0.410-0.934; P = 0.022), whereas high triglycerides (1.653; 95% CI: 1.323-2.064; P < 0.001) followed by previous ischemic disease (1.504; 95% CI: 1.073-2.110; P = 0.018) were the strongest factors associated with low HDL-C. One-third of patients were taking statins at admission, but only 2% were on fibrate therapy. A large increase in statin therapy, but not in other hypolipemiant drug therapy, between admission and discharge was noted in the whole cohort and among patients with low HDL-C. Spanish patients with ACS have a very high prevalence of low HDL-C. Male gender, high triglycerides, and previous ischemic disease are strong, independent factors associated with this disorder. As low HDL-C remains almost completely untreated in ACS, strategies to enhance the treatment of this lipoprotein abnormality are urgently required. Copyright (c) 2010 Wiley Periodicals, Inc.

  8. Paradoxical negative HDL cholesterol response to atorvastatin and simvastatin treatment in Chinese type 2 diabetic patients.

    Science.gov (United States)

    Chang, Yu-Hung; Lin, Kun-Cheng; Chang, Dao-Ming; Hsieh, Chang-Hsun; Lee, Yau-Jiunn

    2013-01-01

    There is extensive but controversial evidence on the diverse effects of statins on the level of high-density lipoprotein cholesterol (HDL-C). Some of these effects may limit the benefits of statins in terms of cardiovascular risk reduction. To identify the conditions for beneficial effects, this study investigated the response to atorvastatin and simvastatin treatment in type 2 diabetic patients with elevated low-density lipoprotein cholesterol (LDL-C). 2,872 subjects with type 2 diabetes from a disease management program were investigated. Patients with LDL-C ≥130 mg/dl or total cholesterol ≥200 mg/dl were put onto statin therapy by the National Health Insurance system in Taiwan. 1,080 patients who completed 1 year of statin treatment were analyzed. There were significant reductions in LDL-C in both the atorvastatin (37.1%) and simvastatin (34.3%) group after one year of treatment compared with baseline levels. Unexpectedly, the majority of diabetic patients who received atorvastatin or simvastatin did not show an increase in HDL-C levels. 59.8% of patients had a significant HDL-C reduction (ΔHDL-C ≤ -3%) after atorvastatin treatment. Multivariate logistic regression analysis showed that the following patients were at higher risk of HDL-C reduction after 12 months: (i) patients in whom statin therapy was initiated aged HDL-C >40 mg/dl, and (iii) female patients with a baseline HDL-C >50 mg/dl. However, diabetic patients with severe atherogenic dyslipidemia (LDL-C ≥130, TG ≥204, and HDL-C ≤34 mg/dl) obtained more benefits in terms of HDL-C change after statin therapy. Diabetic patients, except those with severe atherogenic dyslipidemia, are prone to a decrease in serum HDL-C level after statin treatment, particularly after atorvastatin treatment.

  9. Isomer-specific effects of conjugated linoleic acid on HDL functionality associated with reverse cholesterol transport.

    Science.gov (United States)

    Nicod, Nathalie; Parker, Robert S; Giordano, Elena; Maestro, Virginia; Davalos, Alberto; Visioli, Francesco

    2015-02-01

    High-density lipoproteins (HDLs) are atheroprotective because of their role in reverse cholesterol transport. The intestine is involved in this process because it synthesizes HDL, removes cholesterol from plasma and excretes it into the lumen. We investigated the role of selected dietary fatty acids on intestinal cholesterol uptake and HDL functionality. Caco-2 monolayers grown on Transwells were supplemented with either palmitic, palmitoleic, oleic, linoleic, docosahexaenoic, eicosapentaenoic, arachidonic or conjugated linoleic acids (CLAs): c9,t11-CLA; t9,t11-CLA; c10,t12-CLA. Cells synthesized HDL in the basolateral compartment for 24 h in the absence or presence of an antibody to SR-BI (aSR-BI), which inhibits its interaction with HDL. Free cholesterol (FC) accumulated to a greater extent in the presence than in the absence of aSR-BI, indicating net uptake of FC by SR-BI. Uptake's efficiency was significantly decreased when cells were treated with c9,t11-CLA relative to the other fatty acids. These differences were associated with lower HDL functionality, since neither SR-BI protein expression nor expression and alternative splicing of other genes involved lipid metabolism were affected. Only INSIG2 expression was decreased, with no increase of its target genes. Increasing pre-β-HDL synthesis, by inducing ABCA1 and adding APOA1, resulted in reduced uptake of FC by SR-BI after c9,t11-CLA treatment, indicating reduced functionality of pre-β-HDL. Conversely, treatment with c9,t11-CLA resulted in a greater uptake of FC and esterified cholesterol from mature HDL. Therefore, Caco-2 monolayers administered c9,t11-CLA produced a nonfunctional pre-β-HDL but took up cholesterol more efficiently via SR-BI from mature HDL.

  10. COMPARISION OF BODY MASS INDEX (BMI WITH HIGH DENSITY LIPOPROTEIN (HDL LEVELS IN OBESE PEOPLE

    Directory of Open Access Journals (Sweden)

    Anitha

    2015-11-01

    Full Text Available NTRODUCTION: Cardiovascular disease is a major cause of morbidity and mortality in industrialized nations. Serum lipid concentrations are related to cardiovascular disease risk and one notable association is a statistically significant inverse correlation between HDL-cholesterol concentrations and the probability of developing coronary artery disease. A major related cardiovascular disease risk factor is obesity. Excess body weight is closely linked to low serum HDL-cholesterol concentrations. The general assumption now is that excessive body weight is associated with enlarged adipose tissue deposits, visceral adipose tissue in particular, which in turn are accompanied by elevated serum triacylglycerol concentrations. A well-studied inverse association exists between serum triacylglycerol and HDL-cholesterol concentrations and this may explain the observed low serum HDL-cholesterol concentrations in obesity. This study is done to confirm the above fact. MATERIALS AND METHODS: The subjects for the study were 100 males in the age group of 21 to 40 years. The subjects taken as obese were 50 and those taken as controls were 50. Obesity was taken into account according to the Body Mass Index. RESULTS: Paired T test is done. Results show that 34/50 subjects with BMI 40mg/dl. 40/50 obese patients with BMI >25kg/m2 show HDL levels of <40mg/dl. Significant P value is seen. The study shows that BMI is inversely related to HDL cholesterol levels. DISCUSSION: High HDL cholesterol, above 60 mg/dl is associated with low risk of coronary heart disease. HDL cholesterol below 40 mg/dL is considered too low and appears to be an independent risk factor for coronary artery disease. Low HDL cholesterol is one of the most common phenotypes seen in persons with premature heart disease. Obesity is associated with low HDL cholesterol levels and high triglyceride levels. A negative correlation exists between HDL cholesterol and body-mass index (BMI, meaning that HDL

  11. Coenzyme O*U1*UO, Alpha-Tocopherol and Free Cholesterol in HDL and LDL Fractions

    DEFF Research Database (Denmark)

    Johansen, Kurt; Theorell, Henning; Karlsson, Jan;

    1991-01-01

    Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL......Farmakologi, Alpha-tocopherol, Coenzyme Q*U1*U0, free cholesterol, LDL, Antioxidants, Lipoproteins, HDL...

  12. Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

    NARCIS (Netherlands)

    Kühnast, S.; Fiocco, M.; Hoorn, J.W.A. van der; Princen, H.M.G.; Jukema, J.W.

    2015-01-01

    Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) fai

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

    Science.gov (United States)

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

    2014-10-01

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

  14. Studies on the attachment of fatty acid and N-acetylgalactosamine to mucus glycoprotein nascent chains in rat gastric mucosa

    Energy Technology Data Exchange (ETDEWEB)

    Tsukada, H.; Carter, S.R.; Zielenski, J.; Slomiany, B.L.; Slomiany, A.

    1986-05-01

    The authors have investigated the process of mucin protein acylation and glycosylation to ascertain whether fatty acids and galactosamine are added to nascent chains prior to the completion or after release from the ribosome. For fatty acid and carbohydrate labeling, the rat gastric mucosal cell suspension was incubated with (/sup 3/H) palmitic acid, and (/sup 14/C)-N-acetylgalactosamine for 3h at 37/sup 0/C. After incubation, the cells were washed with incubation medium and subjected to subcellular fractionation. The peptidyl-tRNA was released from polysomes by sedimentation in sucrose gradient containing EDTA (20-30% sucrose gradient). The fraction containing peptidyl-tRNA was dialyzed and nascent chains were separated by ion-exchange chromatography on DEAE-Sephadex. The peptidyl-tRNA, eluted with a linear NaCl gradient was hydrolyzed and separated by SDS-gel electrophoresis and thin-layer chromatography. The individual bands isolated from thin layer plates were analyzed for the content of (/sup 3/H) palmitic acid and (/sup 14/C) N-acetylgalactosamine. The results revealed that fatty acids are incorporated into nascent chains prior to chain completion. Gel electrophoresis and thin layer chromatography showed that the fatty acid moiety is added soon after the acylation site is synthesized on the ribosome, while the GalNAc becomes incorporated only to the acylated peptide.

  15. The influence of solvent and demulsifier additions on nascent froth formation during flotation recovery of Bitumen from Athabasca oil sands

    Energy Technology Data Exchange (ETDEWEB)

    Stasiuk, E.N. [Chemistry Department, University of Calgary, Calgary, AB (Canada); Schramm, L.L. [Petroleum Recovery Institute, Alberta Research Council, 250 Karl Clark Road , T6N 1E4 Edmonton, AB (Canada)

    2001-10-25

    In the commercial slurry conditioning and flotation process applied to Athabasca oil sands the primary bituminous froth can contain significant amounts of emulsified water and suspended solids. Previous work [Fuel Process. Technol. 56 (1998) 243] has shown that a small chemical addition during the nascent froth process can yield froth of higher quality, without sacrificing bitumen recovery or increasing tight emulsion-forming tendency. In the present work we have investigated the addition of demulsifiers, mostly water-in-oil (W/O) emulsion breaking agents, in an attempt to encourage water droplet coalescence and separation from nascent froth. It was found that certain combinations of high HLB surfactants and solvents can be added in small amounts during the nascent froth process to cause significant reductions in froth water content without sacrificing bitumen recovery. The existence of an optimum surfactant concentration for such beneficial additives correlates with a minimum in interfacial tension and is consistent with conventional oilfield demulsifier experience. The application of our results could lead to a substantial increase in the throughput capacity of froth handling and treatment plants.

  16. Beneficial Effect of Higher Dietary Fiber Intake on Plasma HDL-C and TC/HDL-C Ratio among Chinese Rural-to-Urban Migrant Workers

    Directory of Open Access Journals (Sweden)

    Quan Zhou

    2015-04-01

    Full Text Available Research has shown that high-dose supplemental dietary fiber intake has beneficial effects on cardiovascular risk factors. To clarify such a relationship, we examined the association between daily dietary fiber intake and plasma lipids using a cross-sectional design including 1034 (M 502, F 532 rural-to-urban workers in China. We found a dose-response relationship between increased dietary fiber intakes and increase of HDL cholesterol in male workers. There was also a dose-response relationship between increased dietary fiber intake and decreased total cholesterol to HDL cholesterol (TC/HDL-C ratio in both male and female workers, after adjusting for potential confounders (p for trend, all p < 0.05. When the average dietary fiber intake increased from less than 18 g/day to over 30 g/day, the average HDL cholesterol level increased by 10.1%, and the TC/HDL-C ratio decreased by 14.4% for males (p = 0.020 and by 11.1% for females (p = 0.048. In conclusion, higher daily dietary fiber consumption is associated with beneficial effect on cholesterol for rural-to-urban workers in China, suggesting its potential beneficial effect on decreasing the risk of cardiovascular diseases.

  17. Beneficial Effect of Higher Dietary Fiber Intake on Plasma HDL-C and TC/HDL-C Ratio among Chinese Rural-to-Urban Migrant Workers.

    Science.gov (United States)

    Zhou, Quan; Wu, Jiang; Tang, Jie; Wang, Jia-Ji; Lu, Chu-Hong; Wang, Pei-Xi

    2015-04-29

    Research has shown that high-dose supplemental dietary fiber intake has beneficial effects on cardiovascular risk factors. To clarify such a relationship, we examined the association between daily dietary fiber intake and plasma lipids using a cross-sectional design including 1034 (M 502, F 532) rural-to-urban workers in China. We found a dose-response relationship between increased dietary fiber intakes and increase of HDL cholesterol in male workers. There was also a dose-response relationship between increased dietary fiber intake and decreased total cholesterol to HDL cholesterol (TC/HDL-C) ratio in both male and female workers, after adjusting for potential confounders (p for trend, all p dietary fiber intake increased from less than 18 g/day to over 30 g/day, the average HDL cholesterol level increased by 10.1%, and the TC/HDL-C ratio decreased by 14.4% for males (p = 0.020) and by 11.1% for females (p = 0.048). In conclusion, higher daily dietary fiber consumption is associated with beneficial effect on cholesterol for rural-to-urban workers in China, suggesting its potential beneficial effect on decreasing the risk of cardiovascular diseases.

  18. The macrophage and its related cholesterol efflux as a HDL function index in atherosclerosis.

    Science.gov (United States)

    Yamamoto, Suguru; Narita, Ichiei; Kotani, Kazuhiko

    2016-06-01

    The macrophage and its related cholesterol efflux are considered to be a key player in atherosclerotic formation in relation to the function of high-density lipoprotein (HDL). The HDL function can be evaluated by the reaction between lipid-loaded macrophages and lipid-acceptors in the HDL fraction from the plasma, apolipoprotein B-depleted serum, and/or whole serum/plasma. Recent studies have reported that an impaired cholesterol efflux of HDL is observed in patients with cardiometabolic diseases, such as dyslipidemia, diabetes mellitus, and chronic kidney disease. A population-based cohort study has reported an inverse association between the cholesterol efflux capacity of HDL and the incidence of atherosclerotic disease, regardless of the serum HDL-cholesterol level. Moreover, in this paper, when we summarized several clinical interventional studies of statin treatment that examined cholesterol efflux, a potential increase in the efflux in patients treated with statins was implied. However, the effect was not fully defined in the current situation because of the small sample sizes, lack of a unified protocol for measuring the efflux, and short-term intervention periods without cardiovascular outcomes in available studies. Further investigation is necessary to determine the effect of drugs on cholesterol efflux. With additional advanced studies, cholesterol efflux is a promising laboratory index to understand the HDL function.

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

    Science.gov (United States)

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

    2015-09-01

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

  20. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins.

    Science.gov (United States)

    Postmus, Iris; Warren, Helen R; Trompet, Stella; Arsenault, Benoit J; Avery, Christy L; Bis, Joshua C; Chasman, Daniel I; de Keyser, Catherine E; Deshmukh, Harshal A; Evans, Daniel S; Feng, QiPing; Li, Xiaohui; Smit, Roelof A J; Smith, Albert V; Sun, Fangui; Taylor, Kent D; Arnold, Alice M; Barnes, Michael R; Barratt, Bryan J; Betteridge, John; Boekholdt, S Matthijs; Boerwinkle, Eric; Buckley, Brendan M; Chen, Y-D Ida; de Craen, Anton J M; Cummings, Steven R; Denny, Joshua C; Dubé, Marie Pierre; Durrington, Paul N; Eiriksdottir, Gudny; Ford, Ian; Guo, Xiuqing; Harris, Tamara B; Heckbert, Susan R; Hofman, Albert; Hovingh, G Kees; Kastelein, John J P; Launer, Leonore J; Liu, Ching-Ti; Liu, Yongmei; Lumley, Thomas; McKeigue, Paul M; Munroe, Patricia B; Neil, Andrew; Nickerson, Deborah A; Nyberg, Fredrik; O'Brien, Eoin; O'Donnell, Christopher J; Post, Wendy; Poulter, Neil; Vasan, Ramachandran S; Rice, Kenneth; Rich, Stephen S; Rivadeneira, Fernando; Sattar, Naveed; Sever, Peter; Shaw-Hawkins, Sue; Shields, Denis C; Slagboom, P Eline; Smith, Nicholas L; Smith, Joshua D; Sotoodehnia, Nona; Stanton, Alice; Stott, David J; Stricker, Bruno H; Stürmer, Til; Uitterlinden, André G; Wei, Wei-Qi; Westendorp, Rudi G J; Whitsel, Eric A; Wiggins, Kerri L; Wilke, Russell A; Ballantyne, Christie M; Colhoun, Helen M; Cupples, L Adrienne; Franco, Oscar H; Gudnason, Vilmundur; Hitman, Graham; Palmer, Colin N A; Psaty, Bruce M; Ridker, Paul M; Stafford, Jeanette M; Stein, Charles M; Tardif, Jean-Claude; Caulfield, Mark J; Jukema, J Wouter; Rotter, Jerome I; Krauss, Ronald M

    2016-12-01

    In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. We performed a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with pHDL-C response to statin treatment. Based on results from this study that included a relatively large sample size, we suggest that CETP may be the only detectable locus with common genetic variants that influence HDL-C response to statins substantially in individuals of European descent. Although CETP is known to be associated with HDL-C, we provide evidence that this pharmacogenetic effect is independent of its association with baseline HDL-C levels. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly.

    Science.gov (United States)

    Kamada, Yoshihiro; Kida, Sachiho; Hirano, Ken-Ichi; Yamaguchi, Satoshi; Suzuki, Akira; Hashimoto, Chikako; Kimura, Akihiro; Sato, Motoya; Fujii, Hironobu; Sobajima, Tomoaki; Yamamoto, Akiko; Ebisutani, Yusuke; Takamatsu, Shinji; Shinzaki, Shinichiro; Yoshida, Yuichi; Yamada, Makoto; Nagasaka, Hironori; Takehara, Tetsuo; Miyoshi, Eiji

    2016-11-01

    Glycosylation is involved in various pathophysiological conditions. N-Acetylglucosaminyltransferase V (GnT-V), catalyzing β1-6 branching in asparagine-linked oligosaccharides, is one of the most important glycosyltransferases involved in cancer and the immune system. Recent findings indicate that aberrant N-glycan structure can modify lipid metabolism. In this study, we investigated the effects of aberrant glycosylation by GnT-V on high-density lipoprotein cholesterol (HDL) assembly. We used GnT-V transgenic (Tg) mice and GnT-V Hep3B cell (human hepatoma cell line) transfectants. The study also included 96 patients who underwent medical health check-ups. Total serum cholesterol levels, particularly HDL-cholesterol (HDL-C) levels, were significantly increased in Tg vs. wild-type (WT) mice. Hepatic expression of apolipoprotein AI (ApoAI) and ATP-binding cassette subfamily A member 1 (ABCA1), two important factors in HDL assembly, were higher in Tg mice compared with WT mice. ApoAI and ABCA1 were also significantly elevated in GnT-V transfectants compared with mock-transfected cells. Moreover, ApoAI protein in the cultured media of GnT-V transfectants was significantly increased. Finally, we found a strong correlation between serum GnT-V activity and HDL-C concentration in human subjects. Multivariate logistic analyses demonstrated that GnT-V activity was an independent and significant determinant for serum HDL-C levels even adjusted with age and gender differences. Further analyses represented that serum GnT-V activity had strong correlation especially with the large-size HDL particle concentration. These findings indicate that enhanced hepatic GnT-V activity accelerated HDL assembly and could be a novel mechanism for HDL synthesis. Copyright © 2016 the American Physiological Society.

  2. High-density lipoprotein metabolism and reverse cholesterol transport: strategies for raising HDL cholesterol.

    Science.gov (United States)

    Tosheska Trajkovska, Katerina; Topuzovska, Sonja

    2017-08-01

    A key to effective treatment of cardiovascular disease is to understand the body's complex lipoprotein transport system. Reverse cholesterol transport (RCT) is the process of cholesterol movement from the extrahepatic tissues back to the liver. Lipoproteins containing apoA-I [highdensity lipoprotein (HDL)] are key mediators in RCT, whereas non-high-density lipoproteins (non-HDL, lipoproteins containing apoB) are involved in the lipid delivery pathway. HDL particles are heterogeneous; they differ in proportion of proteins and lipids, size, shape, and charge. HDL heterogeneity is the result of the activity of several factors that assemble and remodel HDL particles in plasma: ATP-binding cassette transporter A1 (ABCA1), lecithin cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), hepatic lipase (HL), phospholipid transfer protein (PLTP), endothelial lipase (EL), and scavenger receptor class B type I (SR-BI). The RCT pathway consists of the following steps: 1. Cholesterol efflux from peripheral tissues to plasma, 2. LCAT-mediated esterification of cholesterol and remodeling of HDL particles, 3. direct pathway of HDL cholesterol delivery to the liver, and 4. indirect pathway of HDL cholesterol delivery to the liver via CETP-mediated transfer There are several established strategies for raising HDL cholesterol in humans, such as lifestyle changes; use of drugs including fibrates, statins, and niacin; and new therapeutic approaches. The therapeutic approaches include CETP inhibition, peroxisome proliferator-activated receptor (PPAR) agonists, synthetic farnesoid X receptor agonists, and gene therapy. Results of clinical trials should be awaited before further clinical management of atherosclerotic cardiovascular disease.

  3. Reduced HDL function in children and young adults with type 1 diabetes.

    Science.gov (United States)

    Heier, Martin; Borja, Mark S; Brunborg, Cathrine; Seljeflot, Ingebjørg; Margeirsdottir, Hanna Dis; Hanssen, Kristian F; Dahl-Jørgensen, Knut; Oda, Michael N

    2017-07-06

    Patients with type 1 diabetes (T1D) are at increased risk of cardiovascular disease (CVD). Measures of high-density lipoprotein (HDL) function provide a better risk estimate for future CVD events than serum levels of HDL cholesterol. The objective of this study was to evaluate HDL function in T1D patients shortly after disease onset compared with healthy control subjects. Participants in the atherosclerosis and childhood diabetes study were examined at baseline and after 5 years. At baseline, the cohort included 293 T1D patients with a mean age of 13.7 years and mean HbA1c of 8.4%, along with 111 healthy control subjects. Their HDL function, quantified by HDL-apoA-I exchange (HAE), was assessed at both time points. HAE is a measure of HDL's dynamic property, specifically its ability to release lipid-poor apolipoprotein A-I (apoA-I), an essential step in reverse cholesterol transport. The HAE-apoA-I ratio, reflecting the HDL function per concentration unit apoA-I, was significantly lower in the diabetes group both at baseline, 0.33 (SD = 0.06) versus 0.36 (SD = 0.06) %HAE/mg/dL, p HDL function, quantified as HAE-apoA-I ratio, in children and young adults with T1D compared with healthy control subjects. The differences in HDL function appeared shortly after disease onset and persisted over time.

  4. Influence of HDL particles on cell-cholesterol efflux under various pathological conditions.

    Science.gov (United States)

    Asztalos, Bela F; Horvath, Katalin V; Mehan, Michael; Yokota, Yuya; Schaefer, Ernst J

    2017-06-01

    It has been reported that low cell-cholesterol efflux capacity (CEC) of HDL is an independent risk factor for CVD. To better understand CEC regulation, we measured ABCA1- and scavenger receptor class B type I (SR-BI)-dependent cell-cholesterol efflux, HDL anti-oxidative capacity, HDL particles, lipids, and inflammatory- and oxidative-stress markers in 122 subjects with elevated plasma levels of triglyceride (TG), serum amyloid A (SAA), fibrinogen, myeloperoxidase (MPO), or β-sitosterol and in 146 controls. In controls, there were strong positive correlations between ABCA1-dependent cholesterol efflux and small preβ-1 concentrations (R(2) = 0.317) and SR-BI-dependent cholesterol efflux and large (α-1 + α-2) HDL particle concentrations (R(2) = 0.774). In high-TG patients, both the concentration and the functionality (preβ-1 concentration-normalized ABCA1 efflux) of preβ-1 particles were significantly elevated compared with controls; however, though the concentration of large particles was significantly decreased, their functionality (large HDL concentration-normalized SR-BI efflux) was significantly elevated. High levels of SAA or MPO were not associated with decreased functionality of either the small (preβ-1) or the large (α-1 + α-2) HDL particles. HDL anti-oxidative capacity was negatively influenced by high plasma β-sitosterol levels, but not by the concentrations of HDL particles, TG, SAA, fibrinogen, or MPO. Our data demonstrate that under certain conditions CEC is influenced not only by quantitative (concentration), but also by qualitative (functional) properties of HDL particles. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

  5. Nanocatalyst structure as a template to define chirality of nascent single-walled carbon nanotubes.

    Science.gov (United States)

    Gómez-Gualdrón, Diego A; Zhao, Jin; Balbuena, Perla B

    2011-01-01

    Chirality is a crucial factor in a single-walled carbon nanotube (SWCNT) because it determines its optical and electronic properties. A chiral angle spanning from 0° to 30° results from twisting of the graphene sheet conforming the nanotube wall and is equivalently expressed by chiral indexes (n,m). However, lack of chirality control during SWCNT synthesis is an obstacle for a widespread use of these materials. Here we use first-principles density functional theory (DFT) and classical molecular dynamics (MD) simulations to propose and illustrate basic concepts supporting that the nanocatalyst structure may act as a template to control the chirality during nanotube synthesis. DFT optimizations of metal cluster (Co and Cu)∕cap systems for caps of various chiralities are used to show that an inverse template effect from the nascent carbon nanostructure over the catalyst may exist in floating catalysts; such effect determines a negligible chirality control. Classical MD simulations are used to investigate the influence of a strongly interacting substrate on the structure of a metal nanocatalyst and illustrate how such interaction may help preserve catalyst crystallinity. Finally, DFT optimizations of carbon structures on stepped (211) and (321) cobalt surfaces are used to demonstrate the template effect imparted by the nanocatalyst surface on the growing carbon structure at early stages of nucleation. It is found that depending on the step structure and type of building block (short chains, single atoms, or hexagonal rings), thermodynamics favor armchair or zigzag termination, which provides guidelines for a chirality controlled process based on tuning the catalyst structure and the type of precursor gas.

  6. Roles of histone chaperone CIA/Asf1 in nascent DNA elongation during nucleosome replication.

    Science.gov (United States)

    Ishikawa, Katsuyuki; Ohsumi, Tatsuya; Tada, Shusuke; Natsume, Ryo; Kundu, Lena Rani; Nozaki, Naohito; Senda, Toshiya; Enomoto, Takemi; Horikoshi, Masami; Seki, Masayuki

    2011-10-01

    The nucleosome, which is composed of DNA wrapped around a histone octamer, is a fundamental unit of chromatin and is duplicated during the eukaryotic DNA replication process. The evolutionarily conserved histone chaperone cell cycle gene 1 (CCG1) interacting factor A/anti-silencing function 1 (CIA/Asf1) is involved in histone transfer and nucleosome reassembly during DNA replication. CIA/Asf1 has been reported to split the histone (H3-H4)(2) tetramer into histone H3-H4 dimer(s) in vitro, raising a possibility that, in DNA replication, CIA/Asf1 is involved in nucleosome disassembly and the promotion of semi-conservative histone H3-H4 dimer deposition onto each daughter strand in vivo. Despite numerous studies on the functional roles of CIA/Asf1, its mechanistic role(s) remains elusive because of lack of biochemical analyses. The biochemical studies described here show that a V94R CIA/Asf1 mutant, which lacks histone (H3-H4)(2) tetramer splitting activity, does not form efficiently a quaternary complex with histones H3-H4 and the minichromosome maintenance 2 (Mcm2) subunit of the Mcm2-7 replicative DNA helicase. Interestingly, the mutant enhances nascent DNA strand synthesis in a cell-free chromosomal DNA replication system using Xenopus egg extracts. These results suggest that CIA/Asf1 in the CIA/Asf1-H3-H4-Mcm2 complex, which is considered to be an intermediate in histone transfer during DNA replication, negatively regulates the progression of the replication fork.

  7. HIV-1 Vpu promotes release and prevents endocytosis of nascent retrovirus particles from the plasma membrane.

    Directory of Open Access Journals (Sweden)

    2006-05-01

    Full Text Available The human immunodeficiency virus (HIV type-1 viral protein U (Vpu protein enhances the release of diverse retroviruses from human, but not monkey, cells and is thought to do so by ablating a dominant restriction to particle release. Here, we determined how Vpu expression affects the subcellular distribution of HIV-1 and murine leukemia virus (MLV Gag proteins in human cells where Vpu is, or is not, required for efficient particle release. In HeLa cells, where Vpu enhances HIV-1 and MLV release approximately 10-fold, concentrations of HIV-1 Gag and MLV Gag fused to cyan fluorescent protein (CFP were initially detected at the plasma membrane, but then accumulated over time in early and late endosomes. Endosomal accumulation of Gag-CFP was prevented by Vpu expression and, importantly, inhibition of plasma membrane to early endosome transport by dominant negative mutants of Rab5a, dynamin, and EPS-15. Additionally, accumulation of both HIV and MLV Gag in endosomes required a functional late-budding domain. In human HOS cells, where HIV-1 and MLV release was efficient even in the absence of Vpu, Gag proteins were localized predominantly at the plasma membrane, irrespective of Vpu expression or manipulation of endocytic transport. While these data indicated that Vpu inhibits nascent virion endocytosis, Vpu did not affect transferrin endocytosis. Moreover, inhibition of endocytosis did not restore Vpu-defective HIV-1 release in HeLa cells, but instead resulted in accumulation of mature virions that could be released from the cell surface by protease treatment. Thus, these findings suggest that a specific activity that is present in HeLa cells, but not in HOS cells, and is counteracted by Vpu, traps assembled retrovirus particles at the cell surface. This entrapment leads to subsequent endocytosis by a Rab5a- and clathrin-dependent mechanism and intracellular sequestration of virions in endosomes.

  8. Prox1 identifies proliferating neuroblasts and nascent neurons during neurogenesis in sympathetic ganglia.

    Science.gov (United States)

    Holzmann, Julia; Hennchen, Melanie; Rohrer, Hermann

    2015-12-01

    Neurogenesis in embryonic sympathetic ganglia involves neuroblasts that resume proliferation following neuronal differentiation. As cell cycle exit is not associated with neuronal differentiation, the identity of proliferating neuroblasts is incompletely understood. Here, we use sympathetic ganglia of chick embryos to define the timing of neurogenesis and neuroblast identity focusing on the expression and function of the transcription factor Prox1. We show that a large fraction of neuroblasts has initially withdrawn from the cell cycle at embryonic day 3 (E3), which is reflected by a high proportion of p27(+)/Islet1(+) neuroblasts (63%) and low numbers of EdU(+)/Islet1(+) cells (12%). The proportion of proliferating Islet1(+) neuroblasts, identified by EdU pulse labeling and by the absence of the postmitotic marker p27 increases to reach maximal levels at E5, when virtually all neuroblasts are in the cell cycle (95%). Subsequently, the proportion of EdU-labeled and p27(-) neuroblasts is reduced to reach low levels at E11. Interestingly, the expression of the transcription factor Prox1 is restricted to the neuronal lineage, that is, Sox10(+)/Phox2b(+) neuron progenitors, proliferating p27(-)/Islet1(+) neuroblasts and nascent neurons but is rapidly lost in postmitotic neurons. In vitro and in vivo knockdown and overexpression experiments demonstrate effects of Prox1 in the support of neuroblast proliferation and survival. Taken together, these results define the neurogenesis period in the chick paravertebral sympathetic ganglia including an initial cell cycle withdrawal and identify Prox1 as a marker and regulator of proliferating sympathetic neuroblasts.

  9. HDL and electronegative LDL exchange anti- and pro-inflammatory properties

    OpenAIRE

    Bancells, Cristina; Sánchez-Quesada, José Luis; Birkelund, Ragnhild; Ordóñez-Llanos, Jordi; Benítez, Sònia

    2010-01-01

    Electronegative LDL [LDL(–)] is a minor modified LDL subfraction present in blood with inflammatory effects. One of the antiatherogenic properties of HDL is the inhibition of the deleterious effects of in vitro modified LDL. However, the effect of HDL on the inflammatory activity of LDL(–) isolated from plasma is unknown. We aimed to assess the putative protective role of HDL against the cytokine released induced in monocytes by LDL(–). Our results showed that LDL(–) cytokine release was inhi...

  10. A rapid and precise method for measuring plasma apoE-rich HDL using polyethylene glycol and cation-exchange chromatography: a pilot study on the clinical significance of apoE-rich HDL measurements.

    Science.gov (United States)

    Ikeda, Toru; Shinohata, Ryoko; Murakami, Masaaki; Hina, Kazuyoshi; Kamikawa, Shigeshi; Hirohata, Satoshi; Kusachi, Shozo; Tamura, Arisa; Usui, Shinichi

    2017-02-01

    High-density lipoprotein (HDL) containing apolipoprotein E (apoE-rich HDL) represents only a small portion of plasma HDL. Reliable methods for determining and isolating apoE-rich HDL have not been well studied. We established a novel analytical method for apoE-rich HDL using polyethylene glycol and a cation-exchange column (PEG-column method). Furthermore, we examined biochemical correlates of apoE-rich HDL-cholesterol (HDL-C) in 36 patients who underwent coronary computed tomographic angiography. Our PEG-column method demonstrated high reproducibility (coefficient of variation HDL-C concentrations. Isolated apoE-rich HDL exhibited a larger diameter (14.8nm) than apoE-poor HDL (10.8nm) and contained both apoE and apoA-I. ApoE-rich HDL-C concentrations correlated significantly with triglycerides (rs=-0.646), LDL size (rs=0.472), adiponectin (rs=0.476), and other lipoprotein components. No significant correlation was obtained with the coronary calcium score. Multiple regression analysis revealed that plasma triglycerides and adiponectin concentrations remained significant independent predictors of apoE-rich (adjusted R(2)=0.486) but not apoE-poor HDL-C. The PEG-column method demonstrated, to various degrees, significant correlations between HDL subfractions and several lipid-related biomarkers involved in an atherogenic lipoprotein profile. Our separation technique for apoE-rich HDL is useful to clarify the role of apoE-rich HDL in atherosclerosis. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. THE VLA NASCENT DISK AND MULTIPLICITY SURVEY: FIRST LOOK AT RESOLVED CANDIDATE DISKS AROUND CLASS 0 AND I PROTOSTARS IN THE PERSEUS MOLECULAR CLOUD

    Energy Technology Data Exchange (ETDEWEB)

    Segura-Cox, Dominique M.; Harris, Robert J.; Looney, Leslie W. [Department of Astronomy, University of Illinois, Urbana, IL 61801 (United States); Tobin, John J. [Leiden Observatory, Leiden University, P.O. Box 9513, 2000-RA Leiden (Netherlands); Li, Zhi-Yun [Department of Astronomy, University of Virginia, Charlottesville, VA 22903 (United States); Chandler, Claire; Perez, Laura [National Radio Astronomy Observatory, Socorro, NM 87801 (United States); Kratter, Kaitlin [Steward Observatory, University of Arizona, Tucson, AZ 85721 (United States); Dunham, Michael M. [Harvard-Smithsonian Center for Astrophysics, Cambridge, MA 02138 (United States); Sadavoy, Sarah [Max-Planck-Institut für Astronomie, D-69117 Heidelberg (Germany); Melis, Carl, E-mail: segurac2@illinois.edu [Center for Astrophysics and Space Sciences, University of California, San Diego, CA 92093 (United States)

    2016-02-01

    We present the first dust emission results toward a sample of seven protostellar disk candidates around Class 0 and I sources in the Perseus molecular cloud from the VLA Nascent Disk and Multiplicity (VANDAM) survey with ∼0.″05 or 12 AU resolution. To examine the surface brightness profiles of these sources, we fit the Ka-band 8 mm dust-continuum data in the u, v-plane to a simple, parametrized model based on the Shakura–Sunyaev disk model. The candidate disks are well-fit by a model with a disk-shaped profile and have masses consistent with known Class 0 and I disks. The inner-disk surface densities of the VANDAM candidate disks have shallower density profiles compared to disks around more evolved Class II systems. The best-fit model radii of the seven early-result candidate disks are R{sub c} > 10 AU; at 8 mm, the radii reflect lower limits on the disk size since dust continuum emission is tied to grain size and large grains radially drift inwards. These relatively large disks, if confirmed kinematically, are inconsistent with theoretical models where the disk size is limited by strong magnetic braking to <10 AU at early times.

  12. HDL cholesterol as a predictor for the incidence of lower extremity amputation and wound-related death in patients with diabetic foot ulcers.

    Science.gov (United States)

    Ikura, Kazuki; Hanai, Ko; Shinjyo, Takamichi; Uchigata, Yasuko

    2015-04-01

    We examined whether HDL cholesterol levels are a predictor for an incidence of lower-extremity amputation (LEA) and wound-related death in patients with diabetic foot ulcers (DFUs). This was a single-center, observational, longitudinal historical cohort study of 163 Japanese ambulatory patients with DFUs, 45 woman and 118 men, with a mean (standard deviation) age of 62 (14) years. The primary composite endpoint was defined as the worst of the following outcomes for each individual; (1) minor amputation, defined as amputation below the ankle, (2) major amputation, defined as amputation above the ankle, and (3) wound-related death. During the median follow-up period of 5.1 months, 67 patients (41.1%) reached the endpoint (43 minor amputations, 16 major amputations, and 8 wound-related deaths). In the univariate Cox proportional hazard model analysis, lower HDL cholesterol levels (mmol/L) were significantly associated with the incidence of the primary composite endpoint (hazard ratio 0.16 [95% CI 0.08-0.32], p < 0.001). In the multivariate Cox proportional hazard model analysis using a stepwise variable-selecting procedure, HDL cholesterol levels in addition to the presence of ankle brachial index <0.9 or ≥1.4 and serum albumin levels were selected as independent risk factors for the incidence of the endpoint (hazard ratio 0.30 [95% CI 0.14-0.63], p = 0.002). Similar results were obtained when HDL cholesterol levels were treated as a categorical variable (≥1.03 mmol/L or less). HDL cholesterol levels might be a novel clinical predictor for the incidence of LEA and wound-related death in patients with DFUs. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  13. Effect of insulin analog initiation therapy on LDL/HDL subfraction profile and HDL associated enzymes in type 2 diabetic patients.

    Science.gov (United States)

    Aslan, Ibrahim; Kucuksayan, Ertan; Aslan, Mutay

    2013-04-24

    Insulin treatment can lead to good glycemic control and result in improvement of lipid parameters in type 2 diabetic patients. This study was designed to evaluate the effect of insulin analog initiation therapy on low-density lipoprotein (LDL)/ high-density lipoprotein (HDL) sub-fractions and HDL associated enzymes in type 2 diabetic patients during early phase. Twenty four type 2 diabetic patients with glycosylated hemoglobin (HbA1c) levels above 10% despite ongoing combination therapy with sulphonylurea and metformin were selected. Former treatment regimen was continued for the first day followed by substitution of sulphonylurea therapy with different insulin analogs (0.4 U/kg/day) plus metformin. Glycemic profiles were determined over 72 hours by continuous glucose monitoring system (CGMS) and blood samples were obtained from all patients at 24 and 72 hours. Plasma levels of cholesteryl ester transfer protein (CETP), lecithin-cholesterol acyltransferase (LCAT), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-I) were determined by enzyme-linked immunosorbent assay (ELISA). Measurement of CETP and LCAT activity was performed via fluorometric analysis. Paraoxonase (PON1) enzyme activity was assessed from the rate of enzymatic hydrolysis of phenyl acetate to phenol formation. LDL and HDL subfraction analysis was done by continuous disc polyacrylamide gel electrophoresis. Mean blood glucose, total cholesterol (TC), triglyceride (TG) and very low-density lipoprotein cholesterol (VLDL-C) levels were significantly decreased while HDL-C levels were significantly increased after insulin treatment. Although LDL-C levels were not significantly different before and after insulin initiation therapy a significant increase in LDL-1 subgroup and a significant reduction in atherogenic LDL-3 and LDL-4 subgroups were observed. Insulin analog initiation therapy caused a significant increase in HDL-large, HDL- intermediate and a significant reduction in HDL-small subfractions

  14. Hyperuricemia is Associated with Increased Apo AI Fractional Catabolic Rates and Dysfunctional HDL in New Zealand Rabbits.

    Science.gov (United States)

    Martínez-Ramírez, Miriam; Flores-Castillo, Cristóbal; Sánchez-Lozada, L Gabriela; Bautista-Pérez, Rocío; Carreón-Torres, Elizabeth; Fragoso, José Manuel; Rodriguez-Pérez, José Manuel; García-Arroyo, Fernando E; López-Olmos, Victoria; Luna-Luna, María; Vargas-Alarcón, Gilberto; Franco, Martha; Pérez-Méndez, Oscar

    2017-09-22

    The potential cause-effect relationship between uric acid plasma concentrations and HDL functionality remains elusive. Therefore, this study aimed to explore the effect of oxonic acid (OA)-induced hyperuricemia on the HDL size distribution, lipid content of HDL subclasses, and apo AI turnover, as well as HDL functionality in New Zealand white rabbits. Experimental animals received OA 750 mg/kg/day by oral gavage during 21 days. The HDL-apo AI fractional catabolic rate (FCR) was determined by exogenous labeling with (125)I, and HDL subclasses were determined by sequential ultracentrifugation and PAGE. Paraoxonase-1 activity (PON-1) and the effect of HDL on relaxation of aorta rings in vitro were determined as an indication of HDL functionality. Oxonic acid induced a sixfold increase of uricemia (0.84 ± 0.06 vs. 5.24 ± 0.12 mg/dL, P HDL subclasses, whereas HDL size distribution and HDL-cholesterol remained unchanged. In addition, HDL-apo AI FCR was significantly higher in hyperuricemic rabbits than in the control group (0.03697 ± 0.0038 vs. 0.02605 ± 0.0017 h(-1) respectively, P HDL particles on endothelium-mediated vasodilation. In conclusion, hyperuricemia is associated with structural and metabolic modifications of HDL that result in impaired functionality of these lipoproteins. Our data strongly suggest that uric acid per se exerts deleterious effects on HDL that contribute to increase the risk of atherosclerosis.

  15. ANTIOXIDANT DYSFUNCTIONALITY OF HIGH-DENSITY LIPOPROTEINS (HDL) IN DECOMPENSATED DIABETIC PATIENTS

    National Research Council Canada - National Science Library

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

    2015-01-01

    ... functional activities, including significant anti-inflammatory and antioxidant properties. It has been shown that HDL anti-inflammatory and antioxidant functions are defective in metabolically stable diabetic patients...

  16. Meta-analysis of genome-wide association studies of HDL cholesterol response to statins

    DEFF Research Database (Denmark)

    Postmus, Iris; Warren, Helen R; Trompet, Stella

    2016-01-01

    BACKGROUND: In addition to lowering low density lipoprotein cholesterol (LDL-C), statin therapy also raises high density lipoprotein cholesterol (HDL-C) levels. Inter-individual variation in HDL-C response to statins may be partially explained by genetic variation. METHODS AND RESULTS: We performed...... a meta-analysis of genome-wide association studies (GWAS) to identify variants with an effect on statin-induced high density lipoprotein cholesterol (HDL-C) changes. The 123 most promising signals with p... in an independent group of 10 951 statin-treated individuals, providing a total sample size of 27 720 individuals. The only associations of genome-wide significance (pHDL-C response to statin treatment. CONCLUSIONS: Based on results from this study...

  17. LDL-C/HDL-C异常对脑梗死预后的影响

    Institute of Scientific and Technical Information of China (English)

    王亚琴; 戴其军

    2008-01-01

    目的 探讨LDL-C/HDL-C对脑梗死预后的影响.方法 82例脑梗死患者根据入院检查血LDL-C/HDL-C水平增高组(L1)、正常组(L0),监测1月及3月后LDL-C/HDL-C水平,分别进行mRS、NIHSS评分,立表对比,分析各个指标组间与评分的差异性.结果 发病1月、3月后,mRS及NIHSS评分改善幅度均不及L0组,两组对比有显著性差异(P<0.01).结论 LDL-C/HDL-C比值越大,发病时病情越严重,预后越差.

  18. Discordance of Non-HDL and Directly Measured LDL Cholesterol: Which Lipid Measure is Preferred When Calculated LDL Is Inaccurate?

    OpenAIRE

    Lawrence Baruch; Chiong, Valerie J.; Sanjay Agarwal; Bhanu Gupta

    2013-01-01

    Objective. To determine if non-HDL cholesterol (N-HDL) and directly measured LDL cholesterol (D-LDL) are clinically equivalent measurements. Patients and Methods. Eighty-one subjects recruited for 2 cholesterol treatment studies had at least 1 complete fasting lipid panel and D-LDL performed simultaneously; 64 had a second assessment after 4 to 6 weeks, resulting in 145 triads of C-LDL, D-LDL, and N-HDL. To directly compare N-HDL to D-LDL and C-LDL, we normalized the N-HDL by subtracting 30 f...

  19. Effect of uremia on HDL composition, vascular inflammation, and atherosclerosis in wild-type mice

    DEFF Research Database (Denmark)

    Bang, Christian A; Bro, Susanne; Bartels, Emil D

    2007-01-01

    Wild-type mice normally do not develop atherosclerosis, unless fed cholic acid. Uremia is proinflammatory and increases atherosclerosis 6- to 10-fold in apolipoprotein E-deficient mice. This study examined the effect of uremia on lipoproteins, vascular inflammation, and atherosclerosis in wild...... in cholic acid-fed sham mice. The results suggest that moderate uremia neither induces aortic inflammation nor atherosclerosis in C57BL/6J mice despite increased LDL/HDL cholesterol ratio and altered HDL composition....

  20. How much does HDL cholesterol add to risk estimation? A report from the SCORE Investigators.

    LENUS (Irish Health Repository)

    Cooney, Marie Therese

    2009-06-01

    Systematic COronary Risk Evaluation (SCORE), the risk estimation system recommended by the European guidelines on cardiovascular disease prevention, estimates 10-year risk of cardiovascular disease mortality based on age, sex, country of origin, systolic blood pressure, smoking status and either total cholesterol (TC) or TC\\/high-density lipoprotein cholesterol (HDL-C) ratio. As, counterintuitively, these two systems perform very similarly, we have investigated whether incorporating HDL-C and TC as separate variables improves risk estimation.

  1. Association between triglyceride/HDL cholesterol ratio and carotid atherosclerosis in postmenopausal middle-aged women.

    Science.gov (United States)

    Masson, Walter; Siniawski, Daniel; Lobo, Martín; Molinero, Graciela; Huerín, Melina

    2016-01-01

    The triglyceride/HDL cholesterol ratio, as a surrogate marker of insulin resistance, may be associated to presence of subclinical carotid atherosclerosis in postmenopausal women. The aim of this study was to explore this association. Women (last menstrual period≥2 years) in primary prevention up to 65 years of age were recruited. Association between the triglyceride/HDL cholesterol (HDL-C) ratio and presence of carotid plaque, assessed by ultrasonography, was analyzed. ROC analysis was performed, determining the precision of this ratio to detect carotid plaque. A total of 332 women (age 57±5 years) were recruited. Triglyceride/HDL-C ratio was 2.35±1.6. Prevalence of carotid plaque was 29%. Women with carotid plaque had higher triglyceride/HDL-C ratios (3.33±1.96 vs. 2.1±1.2, P<.001) than women with no carotid plaque. A positive relationship was seen between quintiles of this ratio and prevalence of carotid plaque (p<.001). Regardless of other risk factors, women with higher triglyceride/HDL-C ratios were more likely to have carotid plaque (odds ratio 1.47, 95% confidence interval 1.20-1.79, P<.001). The area under the curve of the triglyceride/HDL-C ratio to detect carotid plaque was .71 (95% confidence interval .65 to .76), and the optimal cut-off point was 2.04. In postmenopausal women in primary prevention, insulin resistance, estimated from the triglyceride/HDL-C ratio, was independently associated to a greater probability of carotid plaque. A value of such ratio greater than 2 may be used for assessing cardiovascular risk in this particular group of women. Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Downregulation of cholesteryl ester transfer protein by glucocorticoids: a randomised study on HDL.

    Science.gov (United States)

    Werumeus Buning, Jorien; Dimova, Lidya G; Perton, Frank G; Tietge, Uwe J F; van Beek, André P; Dullaart, Robin P F

    2017-07-01

    High density lipoprotein (HDL) cholesterol is not decreased in hypercortisolism despite high triglycerides, which may be ascribed to effects on the cholesteryl ester transfer protein (CETP) pathway. We explored if CETP mRNA expression is modulated by glucocorticoid treatment in vitro. Effects of doubling the hydrocortisone (HCT) replacement dose on plasma CETP activity, and HDL characteristics were tested in patients with secondary adrenal insufficiency. Human THP-1 macrophages were incubated with corticosterone in vitro in the presence or absence of a liver X receptor (LXR) agonist, followed by determination of CETP mRNA levels by quantitative real-time PCR. In addition, a randomised double-blind cross-over study was performed in 47 patients with secondary adrenal insufficiency (university medical setting; 10 weeks exposure to a higher HCT dose (0·4-0·6 mg/kg body weight) vs. 10 weeks of a lower HCT dose (0·2-0·3 mg/kg body weight). Corticosterone dose dependently decreased CETP mRNA in THP-1 macrophages. Corticosterone also decreased CETP mRNA expression after LXR pretreatment. In patients, CETP activity decreased with doubling of the HCT dose (P = 0·049), coinciding with an increase in HDL cholesterol, apolipoprotein A-I and the HDL cholesterol/apolipoprotein A-I ratio (reflecting HDL size; P HDL cholesterol/apolipoprotein A-I ratio was correlated with the decrease in plasma CETP activity (r = -0·442, P = 0·002). Glucocorticoids downregulate CETP gene expression in a human macrophage cell system. In line, a higher glucocorticoid replacement dose decreases plasma CETP activity in patients, thereby contributing to higher HDL cholesterol and an increase in estimated HDL size. © 2017 Stichting European Society for Clinical Investigation Journal Foundation.

  3. The effect of HDL-bound and free PON1 on copper-induced LDL oxidation.

    Science.gov (United States)

    Bayrak, Ahmet; Bayrak, Tülin; Bodur, Ebru; Kılınç, Kamer; Demirpençe, Ediz

    2016-09-25

    Oxidative modification of LDL plays an important role in the development of atherosclerosis. High-density lipoprotein (HDL) confers protection against atherosclerosis and the antioxidative properties of paraoxonase 1 (PON1) has been suggested to contribute to this effect of HDL. The PON1 exist in two major polymorphic forms (Q and R), which regulate the concentration and activity of the enzyme and alter its ability to prevent lipid oxidation. However, the association of Q192R polymorphism with PON1's capacity to protect against LDL lipoperoxidation is controversial. The aim of this study was to evaluate the effects of the purified PON1 Q192R and the partially purified HDL-bound PON1 Q192R isoenzymes (HDL-PON1 Q192R) on LDL oxidation, with respect to their arylesterase/homocysteine thiolactonase (HTLase) activities. Cupric ion-induced LDL oxidation was reduced up to 48% by purified PON1 Q192, but only 33% by an equivalent activity of PON1 R192. HDL-PON1 Q192 isoenzyme caused a 65% reduction, whereas HDL-PON1 R192 isoenzyme caused only 46% reduction in copper ion-induced LDL oxidation. These findings reflect the fact that PON1 Q and PON1 R allozymes may have different protective characteristics against LDL oxidation. The protection against LDL oxidation provided by HDL-PON1 Q192R isoenzymes is more prominent than the purified soluble enzymes. Inhibition of the Ca(+2)-dependent PON1 Q192R arylesterase/HTLase by the metal chelator EDTA, did not alter PON1's ability to inhibit LDL oxidation. These studies indicate that the active site involvement of the purified enzyme is not similar to the HDL-bound one, in terms of both PON1 arylesterase/HTLase activity and the protection of LDL from copper ion-induced oxidation. Moreover, PON1's ability to protect LDL from oxidation does not seem to require calcium.

  4. Deep Sequencing of HIV-Infected Cells: Insights into Nascent Transcription and Host-Directed Therapy

    Science.gov (United States)

    Peng, Xinxia; Sova, Pavel; Green, Richard R.; Thomas, Matthew J.; Korth, Marcus J.; Proll, Sean; Xu, Jiabao; Cheng, Yanbing; Yi, Kang; Chen, Li; Peng, Zhiyu; Wang, Jun; Palermo, Robert E.

    2014-01-01

    ABSTRACT Polyadenylated mature mRNAs are the focus of standard transcriptome analyses. However, the profiling of nascent transcripts, which often include nonpolyadenylated RNAs, can unveil novel insights into transcriptional regulation. Here, we separately sequenced total RNAs (Total RNAseq) and mRNAs (mRNAseq) from the same HIV-1-infected human CD4+ T cells. We found that many nonpolyadenylated RNAs were differentially expressed upon HIV-1 infection, and we identified 8 times more differentially expressed genes at 12 h postinfection by Total RNAseq than by mRNAseq. These expression changes were also evident by concurrent changes in introns and were recapitulated by later mRNA changes, revealing an unexpectedly significant delay between transcriptional initiation and mature mRNA production early after HIV-1 infection. We computationally derived and validated the underlying regulatory programs, and we predicted drugs capable of reversing these HIV-1-induced expression changes followed by experimental confirmation. Our results show that combined total and mRNA transcriptome analysis is essential for fully capturing the early host response to virus infection and provide a framework for identifying candidate drugs for host-directed therapy against HIV/AIDS. IMPORTANCE In this study, we used mass sequencing to identify genes differentially expressed in CD4+ T cells during HIV-1 infection. To our surprise, we found many differentially expressed genes early after infection by analyzing both newly transcribed unprocessed pre-mRNAs and fully processed mRNAs, but not by analyzing mRNAs alone, indicating a significant delay between transcription initiation and mRNA production early after HIV-1 infection. These results also show that important findings could be missed by the standard practice of analyzing mRNAs alone. We then derived the regulatory mechanisms driving the observed expression changes using integrative computational analyses. Further, we predicted drugs that

  5. Oxidation-induced loss of the ability of HDL to counteract the inhibitory effect of oxidized LDL on vasorelaxation.

    Science.gov (United States)

    Perségol, Laurence; Brindisi, Marie-Claude; Rageot, David; Pais de Barros, Jean-Paul; Monier, Serge; Vergès, Bruno; Duvillard, Laurence

    2015-11-01

    Several current diseases are associated with an increase in the oxidation of HDL, which is likely to impair their functionality. Our aim was to identify whether oxidation could change the protective effect of HDL against the deleterious effect on vasoreactivity induced by oxidative stress. HDL from healthy subjects were oxidized in vitro by Cu(2+), and the ability of oxidized HDL to counteract the inhibitory effect of oxidized LDL on acetylcholine-induced vasodilation was tested on isolated rabbit aorta rings. Oxidation of HDL was evidenced by the increase in the 7-oxysterols/cholesterol ratio (3.20 ± 1.12 vs 0.02 ± 0.01 % in native HDL, p HDL counteracted this inhibition (E max = 72.4 ± 4.8 vs 50.2 ± 5.0 % p HDL had no effect on oxidized LDL-induced inhibition on endothelium-dependent vasorelaxation (E max = 53.7 ± 4.8 vs 50.2 ± 5.0 %, NS). HDL oxidation is associated with a decreased ability of HDL to remove 7-oxysterols from oxidized LDL. In conclusion, these results show that oxidation of HDL induces the loss of their protective effect against endothelial dysfunction, which could promote atherosclerosis in diseases associated with increased oxidative stress.

  6. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease

    Science.gov (United States)

    Besler, Christian; Heinrich, Kathrin; Rohrer, Lucia; Doerries, Carola; Riwanto, Meliana; Shih, Diana M.; Chroni, Angeliki; Yonekawa, Keiko; Stein, Sokrates; Schaefer, Nicola; Mueller, Maja; Akhmedov, Alexander; Daniil, Georgios; Manes, Costantina; Templin, Christian; Wyss, Christophe; Maier, Willibald; Tanner, Felix C.; Matter, Christian M.; Corti, Roberto; Furlong, Clement; Lusis, Aldons J.; von Eckardstein, Arnold; Fogelman, Alan M.; Lüscher, Thomas F.; Landmesser, Ulf

    2011-01-01

    Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1– and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair–stimulating effects of HDL. PMID:21701070

  7. HDL inhibits the effects of oxidized phospholipids on endothelial cell gene expression via multiple mechanisms[S

    Science.gov (United States)

    Emert, Benjamin; Hasin-Brumshtein, Yehudit; Springstead, James R.; Vakili, Ladan; Berliner, Judith A.; Lusis, Aldons J.

    2014-01-01

    Oxidized 1-palmitoyl-2-arachidonyl-sn-glycero-3-phospholcholine (OxPAPC) and its component phospholipids accumulate in atherosclerotic lesions and regulate the expression of >1,000 genes, many proatherogenic, in human aortic endothelial cells (HAECs). In contrast, there is evidence in the literature that HDL protects the vasculature from inflammatory insult. We have previously shown that in HAECs, HDL attenuates the expression of several proatherogenic genes regulated by OxPAPC and 1-palmitoyl-2-(5,6-epoxyisoprostane E2)-sn-glycero-3-phosphocholine. We now demonstrate that HDL reverses >50% of the OxPAPC transcriptional response. Genes reversed by HDL are enriched for inflammatory and vascular development pathways, while genes not affected by HDL are enriched for oxidative stress response pathways. The protective effect of HDL is partially mimicked by cholesterol repletion and treatment with apoA1 but does not require signaling through scavenger receptor class B type I. Furthermore, our data demonstrate that HDL protection requires direct interaction with OxPAPC. HDL-associated platelet-activating factor acetylhydrolase (PAF-AH) hydrolyzes short-chain bioactive phospholipids in OxPAPC; however, inhibiting PAF-AH activity does not prevent HDL protection. Our results are consistent with HDL sequestering specific bioactive lipids in OxPAPC, thereby preventing their regulation of select target genes. Overall, this work implicates HDL as a major regulator of OxPAPC action in endothelial cells via multiple mechanisms. PMID:24859737

  8. How do elevated triglycerides and low HDL-cholesterol affect inflammation and atherothrombosis?

    Science.gov (United States)

    Welty, Francine K

    2013-09-01

    This review article summarizes recent research into the mechanisms as to how elevated levels of triglyceride (TG) and low levels of high- density- lipoprotein cholesterol (HDL-C) contribute to inflammation and atherosclerosis. Evidence supports the role of TG-rich lipoproteins in signaling mechanisms via apolipoproteins C-III and free fatty acids leading to activation of NFKβ, VCAM-1 and other inflammatory mediators which lead to fatty streak formation and advanced atherosclerosis. Moreover, the cholesterol content in TG-rich lipoproteins has been shown to predict CAD risk better than LDL-C. In addition to reverse cholesterol transport, HDL has many other cardioprotective effects which include regulating immune function. The "functionality" of HDL appears more important than the level of HDL-C. Insulin resistance and central obesity underlie the pathophysiology of elevated TG and low HDL-C in metabolic syndrome and type 2 diabetes. Lifestyle recommendations including exercise and weight loss remain first line therapy in ameliorating insulin resistance and the adverse signaling processes from elevated levels of TG-rich lipoproteins and low HDL-C.

  9. Huntington disease-like 2 (HDL2) in Venezuela: frequency and ethnic origin.

    Science.gov (United States)

    Paradisi, Irene; Ikonomu, Vassiliki; Arias, Sergio

    2013-01-01

    Huntington disease (HD) phenotypes without a HTT mutation are known as HD-like (HDL) syndromes and are caused by mutations in other loci. HDL2, almost indistinguishable from HD, is due to expansions in the Junctophilin 3 locus (JPH3) with a worldwide Sub-Saharan ethnic origin. Sixteen independent patients with involuntary movements, psychiatric disturbances and ataxia not having a HTT mutation were searched for loci PRNP (prion protein, HDL1), JPH3 (HDL2), ATN1 (dentatorubral-pallidoluysian atrophy), ATX2 (spinocerebellar ataxia 2) ATXN3 (spinocerebellar ataxia 3), and TBP (spinocerebellar ataxia 17=HDL4). Markers Duffy, Kell, Diego, D9S1120, plus six JPH3 intragenic single-nucleotide polymorphisms were tested to ascertain ethnic origin. Four unrelated choreic patients had an expanded allele at JPH3. Three of them carried the African marker Duffy null. All four families carried with the mutation the same haplotype most frequent in African populations; Amerindian alleles D9D1120*9 and Diego A; or Kell allele K were absent. HDL2 in Venezuela had a low, but higher relative frequency (2.6%) than that in other Caucasoid populations. It should be searched first in choreic patients not having HTT mutations. The most likely remote ethnic origin for all detected families was African.

  10. Determination of non-HDL cholesterol in diabetic and hypertensive patients.

    Science.gov (United States)

    Contreras, Freddy; Lares, Mary; Castro, Jorge; Velasco, Manuel; Rojas, Joselyn; Guerra, Xavier; Chacín, Maricarmen; Dowling, Victoria; Bermúdez, Valmore

    2010-01-01

    Recently, it has been suggested that non-high-density lipoprotein (non-HDL) cholesterol measure is a useful evaluation tool to assess heart disease death risk. The non-HDL cholesterol is defined as the value between total cholesterol and HDL - total cholesterol, and it involves the different fractions of lipoproteins: low-density lipoprotein, intermediate-density lipoprotein, and very low density lipoprotein, including highly atherogenic lipoproteins as very low density lipoprotein remnants. The purpose of this study was to compare the values of non-HDL cholesterol as a cardiovascular risk marker in a control population, and one diabetic and hypertensive. It was demonstrated that the mean values of non-HDL cholesterol in the diseased groups were higher than the values from the control group, whereas the low-density lipoprotein showed no marked difference in high-risk patients. Non-HDL cholesterol has shown to be a quick and simple way to estimate the risk of developing cardiovascular disease.

  11. Adrenal steroidogenesis disruption caused by HDL/cholesterol suppression in diethylstilbestrol-treated adult male rat.

    Science.gov (United States)

    Haeno, Satoko; Maeda, Naoyuki; Yamaguchi, Kousuke; Sato, Michiko; Uto, Aika; Yokota, Hiroshi

    2016-04-01

    The synthetic estrogen diethylstilbestrol is used to prevent miscarriages and as a therapeutic treatment for prostate cancer, but it has been reported to have adverse effects on endocrine homeostasis. However, the toxicity mechanism is poorly understood. Recently, we reported that diethylstilbestrol impairs adrenal steroidogenesis via cholesterol insufficiency in adult male rats. In the present study, we found that the adrenal cholesterol level was significantly reduced without of the decrease in other precursors in the adrenal steroidogenesis 24 h after a single dose of diethylstilbestrol (0.33 μg/g body mass). The serum HDL/cholesterol level was also reduced only 12 h after the diethylstilbestrol exposure. The level of Apo E, which is indispensable for HDL/cholesterol maturation, was decreased in both the HDL and VLDL/LDL fractions, whereas the level of Apo A1, which is an essential constituent of HDL, was not altered in the HDL fraction. Because the liver is a major source of Apo E and Apo A1, the secretion rates of these proteins were examined using a liver perfusion experiment. The secretion rate of Apo A1 from the liver was consistent between DES-treated and control rats, but that of Apo E was comparatively suppressed in the DES-treated rats. The disruption of adrenal steroidogenesis by diethylstilbestrol was caused by a decrease in serum HDL/cholesterol, which is the main source of adrenal steroidogenesis, due to the inhibition of Apo E secretion from the liver.

  12. Grape Polyphenols Increase the Activity of HDL Enzymes in Old and Obese Rats

    Directory of Open Access Journals (Sweden)

    Andriy L. Zagayko

    2013-01-01

    Full Text Available HDL particles are protein-rich particles that act as a vehicle for reverse cholesterol transport from tissues to the liver. The purpose of this study was to investigate age-dependent changes in the functional activity of HDL and the effect of high-energy diet on this index, as well as to correct it under the influence of grape polyphenols from “Enoant” obtained from Vitis vinifera grapes. We observed the age-dependent composition changes in HDL particle. It was shown that total lipids and triacylglycerol (TG levels were higher in 24-month-old animals. In obese rats, HDL total lipids and TG levels were higher in 24-month-old than in the 3-month-old and 12-month-old groups but did not differ from 24-month-old group. The plasma HDL paraoxonase (PON and lecithin:cholesterol acyltransferase (LCAT activity levels were decreased in old-aged rats, and cholesteryl ester transfer protein (CETP activity was higher in old rats. Keeping 12-month-old animals on high-fructose diet completely leveled the age differences in the data that have been measured between 12-month-old and 24-month-old rats. After “Enoant” administration, an increase of HDL PON and LCAT activity levels and a reduction of CETP activity were found in 24-month-old and obese rats.

  13. A New Predictor for Obstructive Sleep Apnea Syndrome: Monocyte to HDL Ratio.

    Science.gov (United States)

    Atan, Doğan; Kundi, Fatma Cemre Sazak; Özcan, Kürşat Murat; Dere, Hüseyin

    2017-06-01

    The aim of this study was to investigate the relation of serum monocyte to serum HDL cholesterol ratio with obstructive sleep apnea syndrome (OSAS). A total of 336 patients who underwent polysomnography (PSG) were included in this study. The individuals with an apnea hypopnea index (AHI) 5 and excessive daytime sleepiness were included in the study as OSAS patients. OSAS patients were compared with the control group for serum monocyte count, high density lipoprotein (HDL) levels, and monocyte to HDL ratio (MHR). Mild, moderate and severe OSAS subgroups were compared for the same parameters. Additionally, correlations of serum monocyte count, HDL level and MHR with other PSG parameters were analyzed. The mean MHR of control and OSAS groups were 12.90 ± 6.64 and 4.91 ± 6.98, respectively, and the difference was statistically significant (p = 0.041). Mean HDL level of the control group was 47.25 ± 13.61 mg/dL while it was 43.14 ± 13.61 mg/dL in OSAS group (p MHR and HDL levels revealed statistically significant differences (p MHR was higher in OSAS patients compared to the controls. MHR may be a new, useful predictor for OSAS.

  14. Hemorheological and Glycemic Parameters and HDL Cholesterol for the Prediction of Cardiovascular Events

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sung Woo [Division of Cardiology - Department of Internal Medicine - Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Division of Cardiology - Department of Medicine - Samsung Medical Center, Seoul (Korea, Republic of); Kim, Byung Gyu; Kim, Byung Ok; Byun, Young Sup; Goh, Choong Won; Rhee, Kun Joo [Division of Cardiology - Department of Internal Medicine - Sanggye Paik Hospital, Inje University College of Medicine, Seoul (Korea, Republic of); Kwon, Hyuck Moon; Lee, Byoung Kwon, E-mail: cardiobk@yuhs.ac [Division of Cardiology - Department of Internal Medicine - Gangnam Severance Hospital - Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-01-15

    Hemorheological and glycemic parameters and high density lipoprotein (HDL) cholesterol are used as biomarkers of atherosclerosis and thrombosis. To investigate the association and clinical relevance of erythrocyte sedimentation rate (ESR), fibrinogen, fasting glucose, glycated hemoglobin (HbA1c), and HDL cholesterol in the prediction of major adverse cardiovascular events (MACE) and coronary heart disease (CHD) in an outpatient population. 708 stable patients who visited the outpatient department were enrolled and followed for a mean period of 28.5 months. Patients were divided into two groups, patients without MACE and patients with MACE, which included cardiac death, acute myocardial infarction, newly diagnosed CHD, and cerebral vascular accident. We compared hemorheological and glycemic parameters and lipid profiles between the groups. Patients with MACE had significantly higher ESR, fibrinogen, fasting glucose, and HbA1c, while lower HDL cholesterol compared with patients without MACE. High ESR and fibrinogen and low HDL cholesterol significantly increased the risk of MACE in multivariate regression analysis. In patients with MACE, high fibrinogen and HbA1c levels increased the risk of multivessel CHD. Furthermore, ESR and fibrinogen were significantly positively correlated with HbA1c and negatively correlated with HDL cholesterol, however not correlated with fasting glucose. Hemorheological abnormalities, poor glycemic control, and low HDL cholesterol are correlated with each other and could serve as simple and useful surrogate markers and predictors for MACE and CHD in outpatients.

  15. How Do Elevated Triglycerides and Low HDL-Cholesterol Affect Inflammation and Atherothrombosis?

    Science.gov (United States)

    Welty, Francine K.

    2015-01-01

    This review article summarizes recent research into the mechanisms as to how elevated levels of triglyceride (TG) and low levels of high- density- lipoprotein cholesterol (HDL-C) contribute to inflammation and atherosclerosis. Evidence supports the role of TG-rich lipoproteins in signaling mechanisms via apolipoproteins C-III and free fatty acids leading to activation of NFKβ, VCAM-1 and other inflammatory mediators which lead to fatty streak formation and advanced atherosclerosis. Moreover, the cholesterol content in TG-rich lipoproteins has been shown to predict CAD risk better than LDL-C. In addition to reverse cholesterol transport, HDL has many other cardioprotective effects which include regulating immune function. The “functionality” of HDL appears more important than the level of HDL-C. Insulin resistance and central obesity underlie the pathophysiology of elevated TG and low HDL-C in metabolic syndrome and type 2 diabetes. Lifestyle recommendations including exercise and weight loss remain first line therapy in ameliorating insulin resistance and the adverse signaling processes from elevated levels of TG-rich lipoproteins and low HDL-C. PMID:23881582

  16. Lp(a-cholesterol is associated with HDL-cholesterol in overweight and obese African American children and is not an independent risk factor for CVD

    Directory of Open Access Journals (Sweden)

    Sharma Sushma

    2012-01-01

    Full Text Available Abstract Background The role of Lipoprotein (a cholesterol {Lp(a-C}as an additional and/or independent risk factor for cardiovascular disease (CVD is not clear. We evaluated the associations between Lp(a-C and other CVD risk factors including plasma lipoprotein concentrations and body fatness in overweight and obese African American children. Methods A cross-sectional analysis was carried out using data from a sample of 121 African American children aged 9-11 years with Body Mass Index (BMI's greater than the 85th percentile. Body height, weight and waist circumference (WC were measured. Fasting plasma concentrations of Lp(a-C, Total cholesterol (TC, High density lipoprotein cholesterol (HDL-C, Very low density lipoprotein cholesterol (VLDL-C, Intermediate density lipoprotein cholesterol (IDL-C, Low density lipoprotein cholesterol (LDL-C, and Triacylglycerides (TAG were analyzed using the vertical auto profile (VAP cholesterol method. Results After adjusting for child age, gender, and pubertal status, Lp(a-C was positively associated with both HDL-C and TC, and negatively associated with VLDL-C and TAG. Including BMIz and WC as additional covariates did not alter the direction of the relationships between Lp(a-C and the other lipoproteins. Finally, after adjusting for the other plasma lipoproteins, Lp(a-C remained strongly associated with HDL-C, whereas the associations of Lp(a-C with the other lipoproteins were not significant when HDL-C was simultaneously included in the regression models. Conclusions Lp(a-C was positively associated with HDL-C and this association is not influenced by other lipoprotein subclasses or by the degree of obesity. We conclude that Lp(a cholesterol is not an independent risk factor for CVD in African American children.

  17. Identification of GPCR-interacting cytosolic proteins using HDL particles and mass spectrometry-based proteomic approach.

    Directory of Open Access Journals (Sweden)

    Ka Young Chung

    Full Text Available G protein-coupled receptors (GPCRs have critical roles in various physiological and pathophysiological processes, and more than 40% of marketed drugs target GPCRs. Although the canonical downstream target of an agonist-activated GPCR is a G protein heterotrimer; there is a growing body of evidence suggesting that other signaling molecules interact, directly or indirectly, with GPCRs. However, due to the low abundance in the intact cell system and poor solubility of GPCRs, identification of these GPCR-interacting molecules remains challenging. Here, we establish a strategy to overcome these difficulties by using high-density lipoprotein (HDL particles. We used the β(2-adrenergic receptor (β(2AR, a GPCR involved in regulating cardiovascular physiology, as a model system. We reconstituted purified β(2AR in HDL particles, to mimic the plasma membrane environment, and used the reconstituted receptor as bait to pull-down binding partners from rat heart cytosol. A total of 293 proteins were identified in the full agonist-activated β(2AR pull-down, 242 proteins in the inverse agonist-activated β(2AR pull-down, and 210 proteins were commonly identified in both pull-downs. A small subset of the β(2AR-interacting proteins isolated was confirmed by Western blot; three known β(2AR-interacting proteins (Gsα, NHERF-2, and Grb2 and 3 newly identified known β(2AR-interacting proteins (AMPKα, acetyl-CoA carboxylase, and UBC-13. Profiling of the identified proteins showed a clear bias toward intracellular signal transduction pathways, which is consistent with the role of β(2AR as a cell signaling molecule. This study suggests that HDL particle-reconstituted GPCRs can provide an effective platform method for the identification of GPCR binding partners coupled with a mass spectrometry-based proteomic analysis.

  18. High ratio of triglycerides to hdl-cholesterol predicts extensive coronary disease

    Directory of Open Access Journals (Sweden)

    Protasio Lemos da Luz

    2008-01-01

    Full Text Available An abnormal ratio of triglycerides to HDL-cholesterol (TG/HDL-c indicates an atherogenic lipid profile and a risk for the development of coronary disease. OBJECTIVE: To investigate the association between lipid levels, specifically TG/HDL-c, and the extent of coronary disease. METHODS: High-risk patients (n = 374 submitted for coronary angiography had their lipid variables measured and coronary disease extent scored by the Friesinger index. RESULTS: The subjects consisted of 220 males and 154 females, age 57.2 ± 11.1 years, with total cholesterol of 210± 50.3 mg/dL, triglycerides of 173.8 ± 169.8 mg/dL, HDL-cholesterol (HDL-c of 40.1 ± 12.8 mg/dL, LDL-cholesterol (LDL-c of 137.3 ± 46.2 mg/dL, TG/HDL-c of 5.1 ± 5.3, and a Friesinger index of 6.6 ± 4.7. The relationship between the extent of coronary disease (dichotomized by a Friesenger index of 5 and lipid levels (normal vs. abnormal was statistically significant for the following: triglycerides, odds ratio of 2.02 (1.31-3.1; p = 0.0018; HDL-c, odds ratio of 2.21 (1.42-3.43; p = 0.0005; and TG/HDL-c, odds ratio of 2.01(1.30-3.09; p = 0.0018. However, the relationship was not significant between extent of coronary disease and total cholesterol [1.25 (0.82-1.91; p = 0.33] or LDL-c [1.47 (0.96-2.25; p = 0.0842]. The chi-square for linear trends for Friesinger > 4 and lipid quartiles was statistically significant for triglycerides (p = 0.0017, HDL-c (p = 0.0001, and TG/HDL-c (p = 0.0018, but not for total cholesterol (p = 0.393 or LDL-c (p = 0.0568. The multivariate analysis by logistic regression OR gave 1.3 ± 0.79 (p = .0001 for TG/HDL-c, 0.779 ± 0.074 (p = .0001 for HDL-c, and 1.234 ± 0.097 (p = 0.03 for LDL. Analysis of receiver operating characteristic curves showed that only TG/HDL-c and HDL-c were useful for detecting extensive coronary disease, with the former more strongly associated with disease. CONCLUSIONS: Although some lipid variables were associated with the extent of

  19. Remarkable quantitative and qualitative differences in HDL after niacin or fenofibrate therapy in type 2 diabetic patients.

    Science.gov (United States)

    Masana, Luís; Cabré, Anna; Heras, Mercedes; Amigó, Núria; Correig, Xavier; Martínez-Hervás, Sergio; Real, José T; Ascaso, Juan F; Quesada, Helena; Julve, Josep; Palomer, Xavier; Vázquez-Carrera, Manuel; Girona, Josefa; Plana, Núria; Blanco-Vaca, Francisco

    2015-02-01

    HDL-increasing drugs such as fenofibrate and niacin have failed to decrease the cardiovascular risk in patients with type 2 diabetes. Drug-mediated quantitative and qualitative HDL modifications could be involved in these negative results. To evaluate the quantitative and qualitative effects of niacin and fenofibrate on HDL in patients with type 2 diabetes, a prospective, randomised controlled intervention trial was conducted. Thirty type 2 diabetic patients with low HDL were randomised to receive either fenofibrate (FFB) or niacin + laropiprant (ERN/LPR) as an add-on to simvastatin treatment for 12 weeks according to a crossover design. At the basal point and after each intervention period, physical examinations and comprehensive standard biochemical determinations and HDL metabolomics were performed. Thirty nondiabetic patients with normal HDL were used as a basal control group. ERN/LRP, but not FFB, significantly increased HDL cholesterol. Neither ERN/LRP nor FFB reversed the HDL particle size or particle number to normal. ERN/LRP increased apoA-I but not apoA-II, whereas FFB produced the opposite effect. FFB significantly increased Preβ1-HDL, whereas ERN/LRP tended to lower Preβ1-HDL. CETP and LCAT activities were significantly decreased only by ERN/LRP. PAF-AH activity in HDL and plasma decreased with the use of both agents. Despite their different actions on antioxidant parameters, none of the treatments induced detectable antioxidant improvements. ERN/LRP and FFB had strikingly different effects on HDL quantity and quality, as well as on HDL cholesterol concentrations. When prescribing HDL cholesterol increasing drugs, this differential action should be considered.

  20. ApoA-I mutations, L202P and K131del, in HDL from heterozygotes with low HDL-C

    NARCIS (Netherlands)

    Ljunggren, Stefan; Levels, Johannes H. M.; Turkina, Maria V.; Sundberg, Sofie; Bochem, Andrea E.; Hovingh, Kees; Holleboom, Adriaan G.; Lindahl, Mats; Kuivenhoven, Jan Albert; Karlsson, Helen

    PurposeMutations in apolipoprotein A-I (apoA-I) may affect plasma high-density lipoprotein (HDL) cholesterol levels and the risk for cardiovascular disease but little is known about the presence and effects of circulating apoA-I variants. This study investigates whether the apoA-I mutations,

  1. In vivo triglyceride synthesis in subcutaneous adipose tissue of humans correlates with plasma HDL parameters.

    Science.gov (United States)

    Tuvdendorj, Demidmaa; Munoz, Alejandro O; Ruiz-Barros, Viviana; Schwarz, Jean-Marc; Montalto, Giuseppe; Chandalia, Manisha; Sowers, Lawrence C; Rizzo, Manfredi; Murphy, Elizabeth J; Abate, Nicola

    2016-08-01

    Low concentrations of plasma HDL-C are associated with the development of atherosclerotic cardiovascular diseases and type 2 diabetes. Here we aimed to explore the relationship between the in vivo fractional synthesis of triglycerides (fTG) in subcutaneous (s.q.) abdominal adipose tissue (AT), HDL-C concentrations and HDL particle size composition in non-diabetic humans. The fTG in s.q. abdominal AT was measured in 16 non-diabetic volunteers (7 women, 9 men; Age: 49 ± 20 years; BMI: 31 ± 5 kg/m; Fasting Plasma Glucose: 90 ± 10 mg/dl) after (2)H2O labeling. HDL-C concentration and subclasses, large (L-HDL), intermediate (I-HDL) and small (S-HDL) were measured. Linear regression analyses demonstrated significant associations of fTG with plasma concentration of HDL-C (r = 0.625,p = 0.009) and percent contribution of L-HDL (r = 0.798,p HDL (r = -0.765,p HDL (r = -0.629, p = 0.009). When analyses were performed by gender, the associations remained significant in women (HDL-C: r = 0.822,p = 0.023; L-HDL: r = 0.892,p = 0.007; I-HDL: r = -0.927,p = 0.003) but not men. Our study demonstrated an in vivo association between subcutaneous abdominal adipose tissue lipid dynamics and HDL parameters in humans, but this was true for women not men. Positive association with L-HDL and negative with I-HDL suggest that subcutaneous abdominal adipose tissue lipid dynamics may play an important role in production of mature functional HDL particles. Further studies evaluating the mechanism responsible for these associations and the observed gender differences are important and warranted to identify potential novel targets of intervention to increase the production of atheroprotective subclasses of HDL-Cs and thus decreasing the risks of development of atherosclerotic conditions. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. ProAlgaZyme and its subfractions increase plasma HDL cholesterol via upregulation of ApoA1, ABCA1, and SRB1, and inhibition of CETP in hypercholesterolemic hamsters

    Directory of Open Access Journals (Sweden)

    Geamanu A

    2012-06-01

    Full Text Available Andreea Geamanu, Nadia Saadat, Arvind Goja, Monika Wadehra, Xiangming Ji, Smiti V GuptaNutrition and Food Science, Wayne State University, Detroit, MI, USABackground: Plasma HDL cholesterol levels are inversely related to cardiovascular disease, which is the leading cause of death worldwide. This study investigated the effect of an algae infusion, ProAlgaZyme (PAZ, and its subfractions (P1, P2, P3, P4 on plasma HDL in a hamster model.Methods: Sixty male golden Syrian hamsters (8 weeks old were randomized into controls (W or PAZ (P, P1, P2, P3, and P4 (n = 10 per group. An infusion of either 5% (P1, P2, P3 or 20% (P, P4 concentration (v/v was administered via the drinking water for 4 weeks, while the hamsters were being fed a high-fat diet (30% of calories from fat. Serum lipids were assayed and liver samples subjected to reverse transcription polymerase chain reaction to determine the relative transcription levels of genes involved in HDL/reverse cholesterol transport metabolism, ie, ApoA1, ABCA1, CETP, and SRB1.Results: Non-HDL cholesterol was significantly reduced in the P (P < 0.05, P3 and P4 (P < 0.001 groups as compared with the W group, while HDL cholesterol showed a significant increase in the P, P3, and P4 groups (P < 0.001. Moreover, the total cholesterol/HDL ratio was significantly improved in the P, P1, and P2 (P < 0.05, and P3 and P4 (P < 0.001 groups. The shift in cholesterol towards the higher density fractions was validated by density gradient ultracentrifugation. Real-time quantitative polymerase chain reaction showed a significant increase in hepatic ApoA1 (P, P4 and ABCA1 (P3, P4 expression, consistent with an increase in HDL production, biogenesis, and maturation. A two-fold increase in SRB1 expression indicates that P4 further augments the reverse cholesterol transport mechanism. Reduction of CETP expression (P4 is consistent with a decrease in the transfer of cholesteryl ester to LDL, further increasing the amount of

  3. Do chromatin changes around a nascent double strand DNA break spread spherically into linearly non-adjacent chromatin?

    OpenAIRE

    Savic, Velibor

    2013-01-01

    In the last decade, a lot has been done in elucidating the sequence of events that occur at the nascent double strand DNA break. Nevertheless, the overall structure formed by the DNA damage response (DDR) factors around the break site, the repair focus, remains poorly understood. Although most of the data presented so far only address events that occur in chromatin in cis around the break, there are strong indications that in mammalian systems it may also occur in trans, analogous to the rece...

  4. Interactions of Six SNPs in ABCA1gene and Obesity in Low HDL-C Disease in Kazakh of China

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    Ming-hong Yao

    2016-01-01

    Full Text Available Objective: To detect the interactions between six functional polymorphisms in ABCA1 and obesity in Kazakhs with low HDL-C levels. Methods: A total of 204 patients with low HDL-C and 207 health control subjects, which were randomly selected from among 5692 adult Kazakhs, were matched for age and sex. We genotyped ABCA1 single nucleotide polymorphisms of rs2515602, rs3890182, rs2275542, rs2230806, rs1800976, and rs4149313. Results: (1 The genotypic and allelic frequencies of rs2515602, rs2230806 and rs4149313 were different between normal HDL-C and low HDL-C subjects, the genotypic frequency of rs2275542 was also different between normal HDL-C and low HDL-C subjects (p < 0.05; (2 the level of HDL-C (rs2515602 and rs2275542 in normal HDL-C subjects were different among the genotypes (p < 0.05; the levels of TC, LDL-C (rs2515602, rs4149313; TG (rs2515602, rs1800976, rs4149313 in low HDL-C patients were different among the genotypes (p < 0.05; (3 interactions between the rs3890182, rs2275542, rs180096, and rs4149313 polymorphisms in ABCA1 gene and obesity may be associated with low HDL-C disease; (4 the C-C-C-A-A-G, T-C-C-A-A-A, T-C-C-A-A-G, C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes were significant between the subjects with normal HDL-C and low HDL-C level (p < 0.05. Conclusions: The differences in serum lipid levels between normal HDL-C and low HDL-C subjects among Kazakhs might partly result from ABCA1 gene polymorphisms; ABCA1 gene polymorphisms may be associated with low HDL-C disease; the low HDL-C disease might partly result from interactions between ABCA1 gene polymorphisms and obesity; the C-C-C-A-A-G, T-C-C-A-A-A, and T-C-C-A-A-G haplotypes may serve as risk factors of low HDL-C disease among Kazakhs, the C-C-C-A-A-A, C-T-G-G-A-A, and T-T-C-G-A-A haplotypes may serve as protective factor of low HDL-C disease among Kazakhs.

  5. Xuezhikang Therapy Increases miR-33 Expression in Patients with Low HDL-C Levels

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    Ruihua Cao

    2014-01-01

    Full Text Available Background. MicroRNA-33a and -b (miR-33a/b have been revealed to be posttranscriptional regulators of HDL metabolism. Xuezhikang (XZK is a marked natural HDL-raising polypill. We aim to evaluate the effects of XZK on the expression of circulating miR-33a/b in patients with low plasma HDL-C levels. Methods. A total of 42 participating patients with low baseline levels of HDL cholesterol were assigned to receive an XZK capsule, 600 mg twice daily for 6 months. The expression of circulating miR-33a/b was detected at baseline and after XZK therapy measured with quantitative reverse-transcription (RT polymerase chain reaction (PCR. Results. The mean (SD HDL-C level after XZK treatment was 1.19 (0.13 mmol/L, representing an increase of 11.2% from baseline (P<0.001. Q-PCR analysis of plasma miRNAs revealed an increase in relative miR-33a/b expression with XZK treatment. The miR-33a expression was raised from 0.81 to 1.73 (P=0.012; miR-33b expression was increased from 1.2 to 2.75 (P<0.001. The changes of miR-33a and miR-33b were inversely related to the posttreatment LDL-C levels (r=-0.37, P=0.019; r=-0.33, P=0.035, resp.. Conclusion. In patients with low HDL-C levels, XZK therapy raised plasma levels of miR-33a and miR-33b, which may inhibit cellular cholesterol export and limit the HDL-raising effect of XZK.

  6. [Body weight- independent variations in HDL-cholesterol following gastric bypass].

    Science.gov (United States)

    Laguna, S; Andrada, P; Silva, C; Rotellar, F; Valenti, V; Gil, M J; Gómez-Ambrosi, J; Frühbeck, G; Salvador, J

    2016-04-29

    Bariatric surgery has multiple beneficial effects on lipid profile in patients with morbid obesity. However, these changes can be attenuated by weight regain. This retrospective study was designed to assess the effects of gastric bypass(GBP) on different lipid fractions over a 6 year follow-up. We studied 177 patients (135 women)with morbid obesity (BMI 44.2+0.4 kg/m2) aged 42.4+0.9 years before and 3, 6, 9, 12, 24, 36, 48, 60 and 72 months after laparoscopic proximal GBP. Anthropometry, body composition measurement (Bod-Pod) and fasting blood samples were taken in all evaluations to measure total cholesterol (TC),LDL-cholesterol (LDL-C), HDL-cholesterol (HDL-C), triglycerides(TG), glucose and insulin. GPB was followed by a significant BMI reduction (nadir BMI at 18 m 28.3+0.4 kg/m2 pweight and fat mass regain. TG and LDL-C values decreased 30% with respect to preoperative levels, while HDL-C increased 97%over initial values. This HDL-C increase was progressive even over the weight regain phase. Both TC/HDL-C and TG/HDL-Cratios normalized after GBP and values were sustained over the weight regain period until the end of the study. These results confirm the beneficial effects of GBP on all lipid fractions, which are maintained over 6 years of follow-up. Globally, the rise in HDL-C seems to be independent of weight or fat mass changes, since it increases even over the weight regain phase, so contributing to a reduction in the prevalence of dyslipidaemia and to cardiovascular risk reduction.

  7. Fenofibrate, HDL, and cardiovascular disease in Type-2 diabetes: The DAIS trial.

    Science.gov (United States)

    Tsunoda, Fumiyoshi; Asztalos, Ivor B; Horvath, Katalin V; Steiner, George; Schaefer, Ernst J; Asztalos, Bela F

    2016-04-01

    There are conflicting reports on the role of fibrates in CVD-risk. Several studies indicate beneficial effects of fibrates on CVD risk in type-2 diabetic patients. We tested how fenofibrate changes lipoprotein subfractions and glucose homeostasis in type-2 diabetic patients. Selected markers of lipid and glucose homeostasis and inflammation were measured in 204 diabetic patients who participated in the Diabetes Atherosclerosis Intervention Study (DAIS) and were randomly assigned to 200 mg fenofibrate or placebo. Percent changes from baseline until a minimum of 3 years (average 39.6 months) on therapy (end of study) were calculated for all study parameters. The concentrations of total LDL-C and small dense LDL-C (sdLDL-C) did not change on fenofibrate compared to placebo. Compared to placebo, fenofibrate significantly decreased concentrations of triglyceride and remnant-like particle cholesterol (RLP-C) and activity of lipoprotein-associated phospholipase A2 (Lp-PLA2), while significantly increased concentrations of HDL-C. In contrast to other lipid-modifying drugs (e.g. statins) which increase HDL-C by increasing large (α-1) HDL particles, fenofibrate increased HDL-C by increasing the smaller, less antiatherogenic HDL-C particles, α-3 and α-4. Furthermore, despite lowering TG levels by 20%, fenofibrate failed to decrease pre-β1 levels. On fenofibrate, glycated serum-protein levels increased moderately, while insulin and adiponectin levels did not change. On fenofibrate, lipid homeostasis improved and Lp-PLA2 activity decreased while there was no improvement in glucose homeostasis. Despite increasing HDL-C and decreasing triglyceride levels, fenofibrate failed to improve the antiatherogenic properties of the HDL subpopulation profile. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  8. High density lipoprotein (HDL promotes glucose uptake in adipocytes and glycogen synthesis in muscle cells.

    Directory of Open Access Journals (Sweden)

    Qichun Zhang

    Full Text Available BACKGROUND: High density lipoprotein (HDL was reported to decrease plasma glucose and promote insulin secretion in type 2 diabetes patients. This investigation was designed to determine the effects and mechanisms of HDL on glucose uptake in adipocytes and glycogen synthesis in muscle cells. METHODS AND RESULTS: Actions of HDL on glucose uptake and GLUT4 translocation were assessed with 1-[(3H]-2-deoxyglucose and plasma membrane lawn, respectively, in 3T3-L1 adipocytes. Glycogen analysis was performed with amyloglucosidase and glucose oxidase-peroxidase methods in normal and palmitate-treated L6 cells. Small interfering RNA was used to observe role of scavenger receptor type I (SR-BI in glucose uptake of HDL. Corresponding signaling molecules were detected by immunoblotting. HDL stimulated glucose uptake in a time- and concentration-dependent manner in 3T3-L1 adipocytes. GLUT4 translocation was significantly increased by HDL. Glycogen deposition got enhanced in L6 muscle cells paralleling with elevated glycogen synthase kinase3 (GSK3 phosphorylation. Meanwhile, increased phosphorylations of Akt-Ser473 and AMP activated protein kinase (AMPK α were detected in 3T3-L1 adipocytes. Glucose uptake and Akt-Ser473 activation but not AMPK-α were diminished in SR-BI knock-down 3T3-L1 cells. CONCLUSIONS: HDL stimulates glucose uptake in 3T3-L1 adipocytes through enhancing GLUT4 translocation by mechanisms involving PI3K/Akt via SR-BI and AMPK signaling pathways, and increases glycogen deposition in L6 muscle cells through promoting GSK3 phosphorylation.

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

    Science.gov (United States)

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

    2017-02-02

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

  10. Changes in LDL and HDL subclasses in normal pregnancy and associations with birth weight, birth length and head circumference.

    Science.gov (United States)

    Zeljkovic, Aleksandra; Vekic, Jelena; Spasic, Slavica; Jelic-Ivanovic, Zorana; Spasojevic-Kalimanovska, Vesna; Gojkovic, Tamara; Ardalic, Daniela; Mandic-Markovic, Vesna; Cerovic, Nikola; Mikovic, Zeljko

    2013-04-01

    Pregnancy is associated with alterations in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) subclasses, but the exact pattern of these variations remains controversial. This study investigates longitudinal changes of plasma LDL and HDL particles distributions during the course of normal pregnancy, as well as associations of maternal LDL and HDL subclasses distributions before delivery with parameters of newborn size. Blood samples were collected from 41 healthy pregnant women throughout entire pregnancy, before delivery and 7 weeks postpartum. LDL and HDL subclasses were determined by gradient gel electrophoresis, while other biochemical parameters were measured by standard laboratory methods. During gestation LDL size significantly decreased (P LDL I (P LDL II (P HDL size and proportions of HDL 2a particles significantly decreased (P HDL 3b and 3c subclasses (P LDL subclasses distribution during gestation was transient, while postpartum HDL subclasses distribution remained shifted toward smaller particles. Higher proportion of LDL IVB in maternal plasma before delivery was an independent predictor of smaller birth weights and lengths, while higher proportions of LDL IVB and HDL 2a subclasses were independent determinants of newborns' smaller head circumferences. Routine gestational and prenatal care in otherwise normal pregnancy could be complemented with evaluation of LDL and HDL particles distribution in order to ensure an adequate size of the newborn.

  11. Effects of Carbohydrate and Dietary Fiber Intake, Glycemic Index and Glycemic Load on HDL Metabolism in Asian Populations.

    Science.gov (United States)

    Yanai, Hidekatsu; Katsuyama, Hisayuki; Hamasaki, Hidetaka; Abe, Shinichi; Tada, Norio; Sako, Akahito

    2014-10-01

    High-density lipoprotein (HDL) is a lipoprotein which has anti-atherogenic property by reverse cholesterol transport from the peripheral tissues to liver. Low HDL-cholesterol (HDL-C) levels are associated with the development of coronary artery diseases (CADs). Various epidemiological studies have suggested that the development of CAD increase in individuals with less than 40 mg/dL of HDL-C. In spite of accumulation of evidences which suggest a significant association between low HDL-C and cardiovascular diseases, effects of dietary factors on HDL metabolism remained largely unknown. There may be interracial differences in effects of dietary factors on HDL metabolism. Here we reviewed published articles about effects of carbohydrate and dietary fiber intake, glycemic index (GI) and glycemic load (GL), on HDL-C metabolism, regarding meta-analyses and clinical studies performed in Asian population as important articles. Low carbohydrate intake, GI and GL may be beneficially associated with HDL metabolism. Dietary fiber intake may be favorably associated with HDL metabolism in Asian populations.

  12. Lipid regulation in lipodystrophy versus the obesity-associated metabolic syndrome: the dissociation of HDL-C and triglycerides.

    Science.gov (United States)

    Joseph, Jalaja; Shamburek, Robert D; Cochran, Elaine K; Gorden, Phillip; Brown, Rebecca J

    2014-09-01

    There is an inverse relationship between triglycerides and high-density lipoprotein cholesterol (HDL-C) in insulin resistance, such that improvement in insulin resistance decreases triglycerides and increases HDL-C. Patients with lipodystrophy have extreme insulin resistance with high triglycerides and low HDL-C. Leptin replacement in lipodystrophy leads to a marked decrease in triglycerides (∼60%). Our objective was to study the effects of metreleptin on triglycerides and HDL-C in lipodystrophy in contrast to changes in triglycerides and HDL-C in interventions for the obesity-associated metabolic syndrome. This open-label nonrandomized study at the National Institutes of Health included 82 patients with various forms of lipodystrophy. Metreleptin (0.06-0.24 mg/kg/d) was administered for 24 months in lipodystrophy. Serum triglycerides and HDL-C were measured. At baseline, lipodystrophy patients had low HDL-C (30 ± 1 mg/dL) and high triglycerides (961 ± 220 mg/dL) with an inverse relationship between the two (R = -0.37, P = .0006). There was no change in HDL-C with metreleptin despite major improvement in triglycerides, and individual changes in triglycerides only weakly predicted HDL-C change. On linear regression, in obesity, a decrease of 0.1 mg/dL in log(triglycerides) was associated with a 4.2 mg/dL rise in HDL-C, whereas in lipodystrophy, a decrease of 0.1 mg/dL in log(triglycerides) was associated with only a 0.6 mg/dL rise in HDL-C. The normal reciprocal relationship between triglyceride and HDL-C change seen in response to interventions for the obesity-associated metabolic syndrome is quantitatively different from that seen in lipodystrophy in response to metreleptin. Further work is needed to understand HDL-C regulation in this condition.

  13. The association between HDL particle concentration and incident metabolic syndrome in the multi-ethnic Dallas Heart Study.

    Science.gov (United States)

    Mani, Preethi; Ren, Hao-Yu; Neeland, Ian J; McGuire, Darren K; Ayers, Colby R; Khera, Amit; Rohatgi, Anand

    2016-12-12

    Metabolic syndrome (MetS) increases atherosclerotic cardiovascular disease (ASCVD) risk. Low HDL cholesterol (HDL-C) is a diagnostic criterion of MetS and a major ASCVD risk factor. HDL particle concentration (HDL-P) associates with incident ASCVD independent of HDL-C, but its association with incident MetS has not been studied. We hypothesized that HDL-P would be inversely associated with incident metabolic syndrome independent of HDL-C and markers of adiposity and insulin resistance. HDL-P was measured by NMR and visceral fat by MRI in participants of the Dallas Heart Study, a probability-based population sample of adults age 30-65. Participants with prevalent MetS, DM, CVD, and any systemic illlness were excluded. Incident MetS as defined by NCEP ATPIII criteria was determined in all participants after median follow-up period of 7.0 years. Among 1120 participants without DM or MetS at baseline (57% women, 45% Black, mean age 43), 22.8% had incident MetS at follow-up. HDL-P and HDL-C were modestly correlated (r=0.54, pHDL-C ratio, and HOMA-IR, the lowest quartile of HDL-P was associated with a 2-fold increased risk of incident MetS (OR 2.1, 95%CI 1.4-3.1; p=0.0003). Low HDL-P is independently associated with incident MetS after adjustment for traditional risk factors, lipid parameters, adiposity, inflammation, and markers of insulin resistance. Further studies are warranted to validate these findings and elucidate the mechanisms underpinning this association. Copyright © 2016. Published by Elsevier Ltd.

  14. Diabetic HDL Is Dysfunctional in Stimulating Endothelial Cell Migration and Proliferation Due to Down Regulation of SR-BI Expression

    Science.gov (United States)

    Pan, Bing; Ma, Yijing; Ren, Hui; He, Yubin; Wang, Yongyu; Lv, Xiaofeng; Liu, Donghui; Ji, Liang; Yu, Baoqi; Wang, Yuhui; Chen, Y. Eugene; Pennathur, Subramaniam; Smith, Jonathan D.; Liu, George; Zheng, Lemin

    2012-01-01

    Background Diabetic HDL had diminished capacity to stimulate endothelial cell (EC) proliferation, migration, and adhesion to extracellular matrix. The mechanism of such dysfunction is poorly understood and we therefore sought to determine the mechanistic features of diabetic HDL dysfunction. Methodology/Principal Findings We found that the dysfunction of diabetic HDL on human umbilical vein endothelial cells (HUVECs) was associated with the down regulation of the HDL receptor protein, SR-BI. Akt-phosphorylation in HUVECs was induced in a biphasic manner by normal HDL. While diabetic HDL induced Akt phosphorylation normally after 20 minutes, the phosphorylation observed 24 hours after diabetic HDL treatment was reduced. To determine the role of SR-BI down regulation on diminished EC responses of diabetic HDL, Mouse aortic endothelial cells (MAECs) were isolated from wild type and SR-BI (−/−) mice, and treated with normal and diabetic HDL. The proliferative and migratory effects of normal HDL on wild type MAECs were greatly diminished in SR-BI (−/−) cells. In contrast, response to diabetic HDL was impaired in both types suggesting diminished effectiveness of diabetic HDL on EC proliferation and migration might be due to the down regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. Conclusions/Significance Diabetic HDL was dysfunctional in promoting EC proliferation, migration, and adhesion to matrix which was associated with the down-regulation of SR-BI. Additionally, SR-BI down regulation diminishes diabetic HDL’s capacity to activate Akt chronically. PMID:23133640

  15. Subclasses of Serum HDL in Hyperlipidemia%高脂血症患者血清HDL亚类的组成

    Institute of Scientific and Technical Information of China (English)

    徐燕华; 傅明德; 刘秉文; 徐勇霞; 姚佳; 张雪梅

    2003-01-01

    目的探讨高脂血症患者血清HDL亚类组成和相对百分含量的变化及其与血脂水平的关系. 方法采用双向电泳-免疫印迹检测法分析168例高脂血症患者血清HDL亚类组成及相对百分含量. 结果高脂血症患者血清中前β1-HDL、前β2-HDL、HDL3c、HDL3b及HDL3a含量显著增加(P均<0.01或<0.05),而HDL2a及HDL2b含量显著减少(P<0.01).高脂血症患者中男性前β1-HDL及HDL3b含量显著高于女性(P<0.01),HDL2a及HDL2b含量显著低于女性(P<0.01).正常对照者中男性前β1-HDL含量显著高于女性(P<0.05),HDL2b含量显著低于女性(P<0.05).高脂血症患者血清TG含量与前β1-HDL、前β2-HDL、HDL3b及HDL3a水平呈正相关(r=0.583、r=0.196、r=0.130及r=0.370),而与HDL2a及HDL2b水平呈负相关(r=-0.293及r=-0.456);TC含量与前β1-HDL及HDL3b水平呈正相关(r=0.348及r=0.219),而与HDL2b水平呈负相关(r=-0.276);LDL-C含量与HDL3b水平呈正相关(r=0.187);HDL-C含量与前β1-HDL及HDL3a水平呈负相关(r=-0.354及r=-0.292),而与HDL2a及HDL2b(r=0.254及r=0.256)水平呈负相关.TG/HDL-C比值与前β1-HDL、前β2-HDL、HDL3b及HDL3a水平呈正相关(r=0.593、r=0.225、r=0.123及r=0.394),而与HDL2a及HDL2b水平呈负相关(r=-0.317及r=-0.459). 结论高脂血症患者血清HDL颗粒直径呈变小趋势,提示其HDL成熟代谢过程受阻.高脂血症患者血清HDL亚类的变化趋势可能与冠心病具有密切的相关性.

  16. Translation initiation factor (iso) 4E interacts with BTF3, the beta subunit of the nascent polypeptide-associated complex.

    Science.gov (United States)

    Freire, Miguel Angel

    2005-01-31

    A two-hybrid screen with the translation initiation factor, eIF(iso)4E from Arabidopsis, identified a clone encoding a lipoxygenase type 2 [Freire, M.A., et al., 2000. Plant lipoxygenase 2 is a translation initiation factor-4E-binding protein. Plant Molecular Biology 44, 129-140], and three cDNA clones encoding the homologue of the mammalian BTF3 factor, the beta subunit of the nascent polypeptide-associated complex (NAC). Here we report on the interaction between the translation initiation factor eIF(iso)4E and AtBTF3. AtBTF3 protein is able to interact with the wheat initiation factors eIF4E and eIF(iso)4E. AtBTF3 contains a sequence related to the prototypic motif found on most of the 4E-binding proteins, and competes with the translation initiation factor eIF(iso)4G for eIF4(iso)4E binding, in a two hybrid interference assay. These findings provide a molecular link between the translation initiation mechanism and the emergence of the nascent polypeptide chains.

  17. Actualización en el manejo del colesterol hdl bajo

    Directory of Open Access Journals (Sweden)

    Rigotti R. Attilio, Dr.

    2012-11-01

    Full Text Available Los niveles plasmáticos bajos de colesterol transportado en las lipoproteínas de alta densidad (HDL constituyen un elemento independiente de riesgo cardiovascular ateroesclerótico. Algunos protocolos clínicos enfocados en el manejo farmacológico de los niveles bajos de colesterol HDL en pacientes de alto riesgo cardiovascular han mostrado resultados favorables. Por otro lado, existen nuevas formulaciones de la niacina, el agente farmacológico disponible más efectivo para el manejo del colesterol HDL bajo, y se están desarrollando nuevos fármacos más potentes para aumentar los niveles plasmáticos de colesterol HDL. En el futuro, nuevos medicamentos que modulen el metabolismo de HDL y demuestren beneficio sobre el control del riesgo cardiovascular ateroesclerótico, podrían mejorar aún más el manejo actual de esta condición patológica que se basa esencialmente en el uso de estatinas.

  18. The Challenging to Increase HDL-C: the different machanisms and effects evaluation%升高高密度脂蛋白胆固醇(HDL-C)面临的挑战——升HDL-C药物的不同机制和HDL-C升高的疗效评价

    Institute of Scientific and Technical Information of China (English)

    曲鹏; 王虹艳

    2008-01-01

    高密度脂蛋白胆固醇(HDL-C)水平与发生冠心病的危险性呈负相关.HDL通过促进胆固醇逆转运、改善内皮功能、抗氧化、抗炎和抗血栓而发挥心血管保护作用.HDL已成为冠心病防治工作的新靶点,生活方式和调脂药物的干预能升高HDL-C,然而HDL的功能比HDL-C血浆水平更重要,多项以HDL为靶点新的治疗措施正在研究中,临床上如何评价HDL-C升高的疗效价值及升高HDL-C的药物和策略有着重要意叉.进一步研究HDL的结构、代谢和功能能够深入了解脂质代谢过程和动脉粥样硬化发生机制,使干预HDL成为动脉粥样硬化防治新的目标.

  19. Combination of estrogen replacement and exercise protects against HDL oxidation in post-menopausal women.

    Science.gov (United States)

    Lawler, J M; Hu, Z; Green, J S; Crouse, S F; Grandjean, P W; Bounds, R G

    2002-10-01

    The incidence of atherosclerosis and cardiovascular disease (CVD) in women increases following menopause and has been associated with a reduction in circulating estrogen. Increased CVD risk is also perpetuated by sedentary lifestyle. Growing evidence indicates that oxidation of lipoproteins leads to a powerful immune response, disruption of normal lipoprotein function, and deposition of atherosclerotic plaques. For example, once high-density lipoproteins (HDL) are oxidized, they lose the ability to a) participate in reverse transport of cholesterol to the liver, and b) protect low-density lipoproteins (LDL) against oxidation. The purpose of this study was to determine the effects of combining estrogen replacement and exercise upon lipid peroxidation of the HDL fraction (HDL-ox). Blood samples were drawn from 34 post-menopausal women from four groups: women who were not receiving estrogen replacement and who were sedentary (NSD) (n = 9); women who were not receiving estrogen replacement and who were participating in regular exercise (NEX) (n = 8); women who were receiving estrogen replacement and who were sedentary (ESD) (n = 8); and women who were receiving estrogen replacement and who were participating in regular exercise (EEX) (n = 9). Total-HDL cholesterol was significantly higher (pexercise in post-menopausal women may be most effective in reducing oxidation of HDL in vivo.

  20. MediterrAsian Diet Products That Could Raise HDL-Cholesterol: A Systematic Review

    Science.gov (United States)

    Giacosa, Attilio; Morazzoni, Paolo; Guido, Davide; Grassi, Mario; Morandi, Gabriella; Bologna, Chiara; Allegrini, Pietro

    2016-01-01

    Background. High HDL-cholesterol (HDL-C) values are negatively correlated with cardiovascular diseases. This review analyses the effect of the supplementation with various Mediterranean diet products (artichoke, bergamot, and olive oil) and Asian diet products (red yeast rice) on the HDL-C value in dyslipidemic subjects. Methods. A systematic review has been done involving all the English written studies published from the 1st of January 1958 to the 31st of March 2016. Results. The results of this systematic review indicate that the dietary supplementation with red yeast rice, bergamot, artichoke, and virgin olive oil has promising effects on the increase of HDL-C serum levels. The artichoke leaf extract and virgin olive oil appear to be particularly interesting, while bergamot extract needs further research and the effect of red yeast rice seems to be limited to patients with previous myocardial infarction. Conclusions. Various MediterrAsian diet products or natural extracts may represent a potential intervention treatment to raise HDL-C in dyslipidemic subjects. PMID:27882320

  1. MediterrAsian Diet Products That Could Raise HDL-Cholesterol: A Systematic Review.

    Science.gov (United States)

    Rondanelli, Mariangela; Giacosa, Attilio; Morazzoni, Paolo; Guido, Davide; Grassi, Mario; Morandi, Gabriella; Bologna, Chiara; Riva, Antonella; Allegrini, Pietro; Perna, Simone

    2016-01-01

    Background. High HDL-cholesterol (HDL-C) values are negatively correlated with cardiovascular diseases. This review analyses the effect of the supplementation with various Mediterranean diet products (artichoke, bergamot, and olive oil) and Asian diet products (red yeast rice) on the HDL-C value in dyslipidemic subjects. Methods. A systematic review has been done involving all the English written studies published from the 1st of January 1958 to the 31st of March 2016. Results. The results of this systematic review indicate that the dietary supplementation with red yeast rice, bergamot, artichoke, and virgin olive oil has promising effects on the increase of HDL-C serum levels. The artichoke leaf extract and virgin olive oil appear to be particularly interesting, while bergamot extract needs further research and the effect of red yeast rice seems to be limited to patients with previous myocardial infarction. Conclusions. Various MediterrAsian diet products or natural extracts may represent a potential intervention treatment to raise HDL-C in dyslipidemic subjects.

  2. MediterrAsian Diet Products That Could Raise HDL-Cholesterol: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Mariangela Rondanelli

    2016-01-01

    Full Text Available Background. High HDL-cholesterol (HDL-C values are negatively correlated with cardiovascular diseases. This review analyses the effect of the supplementation with various Mediterranean diet products (artichoke, bergamot, and olive oil and Asian diet products (red yeast rice on the HDL-C value in dyslipidemic subjects. Methods. A systematic review has been done involving all the English written studies published from the 1st of January 1958 to the 31st of March 2016. Results. The results of this systematic review indicate that the dietary supplementation with red yeast rice, bergamot, artichoke, and virgin olive oil has promising effects on the increase of HDL-C serum levels. The artichoke leaf extract and virgin olive oil appear to be particularly interesting, while bergamot extract needs further research and the effect of red yeast rice seems to be limited to patients with previous myocardial infarction. Conclusions. Various MediterrAsian diet products or natural extracts may represent a potential intervention treatment to raise HDL-C in dyslipidemic subjects.

  3. 急性脑梗死患者LDL-C/HDL-C比值的变化

    Institute of Scientific and Technical Information of China (English)

    彭敏

    2016-01-01

    目的:探讨 LDL-C/HDL-C 比值与急性脑梗死患者危险因素的关系及对预后的预测价值。方法:选取急性脑梗死患者38例(梗死组)及同期在我院体检的健康人44例(对照组),分别检测其血浆 LDL、HDL 水平并计算其比值,统计其一般资料和危险因素,并随访1~2年。结果:梗死组的 LDL-C/HDL-C 高于对照组(P0.6的患者不良事件发生率高于 LDL-C/HDL-C<0.6的患者(χ2=12.42,P<0.05)。 LDL-C/HDL-C 比值与不良预后的发生率呈正相关(r=0.68,P<0.05)。结论:LDL/HDL比值是急性脑梗死的独立危险因素,与预后不良事件呈正相关。

  4. LDL-C、HDL-C和IMT与动脉粥样硬化的关系

    Institute of Scientific and Technical Information of China (English)

    胡军

    2013-01-01

    目的 探讨低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)和颈动脉内中膜厚度(IMT)与动脉粥样硬化(AS)的关系.方法 选取本院2008年6月至2011年6月住院健康体检者120例,其中男78例,女42例,年龄在20岁85之间,平均(50.6±11.5)岁.采用日立7020型全自动生化仪检测患者LDL-C、HDL-C含量;采用日本东芝SSA-520A超声诊断仪测量颈动脉内中膜厚度(IMT);采用SPSS 16.0统计学软件对结果进行分析.结果 动脉粥样硬化患者的LDL-C、HDL-C和IMT与健康对照组相比均差异有统计学意义(P<0.05),LDL-C与AS呈负相关、HDL-C、IMT与AS呈正相关.结论 LDL-C、HDL-C和IMT的是预防动脉粥样硬化疾病的有效指标.

  5. Cell lipid metabolism modulators 2-bromopalmitate, D609, monensin, U18666A and probucol shift discoidal HDL formation to the smaller-sized particles: implications for the mechanism of HDL assembly.

    Science.gov (United States)

    Quach, Duyen; Vitali, Cecilia; La, Fiona M; Xiao, Angel X; Millar, John S; Tang, Chongren; Rader, Daniel J; Phillips, Michael C; Lyssenko, Nicholas N

    2016-12-01

    ATP-binding cassette transporter A1 (ABCA1) mediates formation of disc-shaped high-density lipoprotein (HDL) from cell lipid and lipid-free apolipoprotein A-I (apo A-I). Discoidal HDL particles are heterogeneous in physicochemical characteristics for reasons that are understood incompletely. Discoidal lipoprotein particles similar in characteristics and heterogeneity to cell-formed discoidal HDL can be reconstituted from purified lipids and apo A-I by cell-free, physicochemical methods. The heterogeneity of reconstituted HDL (rHDL) is sensitive to the lipid composition of the starting lipid/apo A-I mixture. To determine whether the heterogeneity of cell-formed HDL is similarly sensitive to changes in cell lipids, we investigated four compounds that have well-established effects on cell lipid metabolism and ABCA1-mediated cell cholesterol efflux. 2-Bromopalmitate, D609, monensin and U18666A decreased formation of the larger-sized, but dramatically increased formation of the smaller-sized HDL. 2-Bromopalmitate did not appear to affect ABCA1 activity, subcellular localization or oligomerization, but induced dissolution of the cholesterol-phospholipid complexes in the plasma membrane. Arachidonic and linoleic acids shifted HDL formation to the smaller-sized species. Tangier disease mutations and inhibitors of ABCA1 activity wheat germ agglutinin and AG 490 reduced formation of both larger-sized and smaller-sized HDL. The effect of probucol was similar to the effect of 2-bromopalmitate. Taking rHDL formation as a paradigm, we propose that ABCA1 mutations and activity inhibitors reduce the amount of cell lipid available for HDL formation, and the compounds in the 2-bromopalmitate group and the polyunsaturated fatty acids change cell lipid composition from one that favors formation of the larger-sized HDL particles to one that favors formation of the smaller-sized species. Copyright © 2016 Elsevier B.V. All rights reserved.

  6. Observations of HDL components in female probands following an ultra-long distance run of 100 miles.

    Science.gov (United States)

    Schriewer, H; Jung, K; Emke, F; Assmann, G

    1985-01-01

    The serum concentrations of total cholesterol and triglycerides as well as the cholesterol, phosphatidyl choline, and apolipoprotein components of HDL were tested in 19 participants immediately before and immediately after a 100-mile run. After the run, taking into account any alterations in total protein, the following changes were observed: a decrease in total cholesterol (p less than 0.001), as well as in triglycerides (p less than 0.05), and an increase in HDL cholesterol (p less than 0.05), and HDL phosphatidyl choline (p less than 0.01). The concentrations of HDL apolipoprotein A-I and HDL apolipoprotein A-II were not affected. The results indicate a change in composition of HDL following extreme prolonged physical exercise in women.

  7. Mutation in APOA1 predicts increased risk of ischaemic heart disease and total mortality without low HDL cholesterol levels

    DEFF Research Database (Denmark)

    Haase, C L; Frikke-Schmidt, R; Nordestgaard, B G

    2011-01-01

    OBJECTIVES: To determine whether mutations in APOA1 affect levels of high-density lipoprotein (HDL) cholesterol and to predict risk of ischaemic heart disease (IHD) and total mortality in the general population. BACKGROUND: Epidemiologically, risk of IHD is inversely related to HDL cholesterol...... levels. Mutations in apolipoprotein (apo) A-I, the major protein constituent of HDL, might be associated with low HDL cholesterol and predispose to IHD and early death. DESIGN: We resequenced APOA1 in 190 individuals and examined the effect of mutations on HDL cholesterol, risk of IHD, myocardial......164S heterozygotes had normal plasma lipid and lipoprotein levels, including HDL cholesterol and apoA-I, and this finding was confirmed in adenovirus-transfected mice. CONCLUSIONS: A164S is the first mutation in APOA1 to be described that predicts an increased risk of IHD, MI and total mortality...

  8. Relationship Between HDL-C Level of Serum and Prognosis of Essential Hypertension%血清HDL-C水平与原发性高血压预后的关系

    Institute of Scientific and Technical Information of China (English)

    林小凤; 黄维超

    2015-01-01

    目的 探讨血清高密度脂蛋白(HDL-C)水平与原发性高血压(EH)预后的关系.方法 选取我院收治的EH患者110例作为研究对象,根据血清HDL-C水平分为HDL-C水平减低组(52例)和HDL-C水平正常组(58例),检测两组患者血脂、血压、动脉内膜中膜厚度(IMT)等,随访2年观察预后.结果 HDL-C水平正常组血压、血脂、IMT、BMI均优于HDL-C水平低下组,差异均具有统计学意义(P<0.05);HDL-C水平正常组心肌缺血、心绞痛、脑血管意外的发生率分别为25.86%、17.24%、15.52%,均显著低于HDL-C水平低下组,差异具有统计学意义(P<0.05).结论 EH合并血清HDL-C水平低下会增加EH患者心血管事件的发生率,诱发不良预后.

  9. Dyslipidemia, but not hyperglycemia and insulin resistance, is associated with marked alterations in the HDL lipidome in type 2 diabetic subjects in the DIWA cohort: impact on small HDL particles.

    Science.gov (United States)

    Ståhlman, Marcus; Fagerberg, Björn; Adiels, Martin; Ekroos, Kim; Chapman, John M; Kontush, Anatol; Borén, Jan

    2013-11-01

    In this study we have used mass spectrometry in order to characterize the HDL lipidome in three groups of women from the DIWA cohort; one control group, plus two groups with type 2 diabetes with insulin resistance; one dyslipidemic and one normolipidemic. The aim was to investigate whether dyslipidemia is required in addition to insulin resistance for the occurrence of an altered HDL lipidome, which in turn might impact HDL functionality. The dyslipidemic type 2 diabetic subjects were distinguished by obesity, hypertriglyceridemia with elevated apoC3, low HDL-cholesterol and chronic low grade inflammation. In a stepwise multivariate linear regression analysis, including biomarkers of dyslipidemia and insulin resistance as independent variables, only dyslipidemia showed a significant correlation with HDL lipid classes. Small HDL-particles predominated in dyslipidemic subjects in contrast to the normolipidemic diabetic and control groups, and were enriched in lysophosphatidylcholine (+13%), a product of proinflammatory phospholipases, and equally in two core lipids, palmitate-rich triacylglycerols and diacylglycerols (+77 %), thereby reflecting elevated CETP activity. Dyslipidemic small HDL particles were further distinguished not only as the primary carrier of ceramides, which promote inflammation and insulin resistance, but also by a subnormal plasmalogen/apoAI ratio, consistent with elevated oxidative stress typical of type 2 diabetes. From these data we conclude that in type 2 diabetes, dyslipidemia predominates relative to hyperglycemia for the occurrence of an altered HDL lipidome. Furthermore, dyslipidemia alters the cargo of bioactive lipids, with implications for HDL function. © 2013.

  10. 影响HDL-CH检测结果准确性的因素

    Institute of Scientific and Technical Information of China (English)

    郭丽宏

    2001-01-01

    @@ HDL被认为是一种抗动脉粥样硬化的脂蛋白,冠心病的保护因子.HDL-ch含量与动脉管腔狭窄程度呈显著的负相关.在估计心血管的危险因子中HDL-ch的临床意义比胆固醇和甘油三酯高.HDL-ch具有心血管上带走总胆固醇和LDL-ch的作用.故需设法提高结果的准确性,有一定的临床意义. ……

  11. 沉淀法与直接法HDL-c和LDL-c测定研究

    Institute of Scientific and Technical Information of China (English)

    许希红

    2007-01-01

    目的对直接法和沉淀法测定HDL-c和LDL-c两种测定方法进行比较。方法采用直接法(聚阴离子多聚物/表面活性剂法)与沉淀法(PTA-Mg2+法、PVS法)对92例随机门诊病人分别进行HDL-c和LDL-c测定。结果HDL-c测定两种方法无差别;LDL-c测定两种方法差异显著。结论直接法比沉淀法操作更简便,影响因素少,更适于临床。

  12. Imaging and force measurement of LDL and HDL by AFM in air and liquid.

    Science.gov (United States)

    Gan, Chaoye; Ao, Meiying; Liu, Zhanghua; Chen, Yong

    2015-01-01

    The size and biomechanical properties of lipoproteins are tightly correlated with their structures/functions. While atomic force microscopy (AFM) has been used to image lipoproteins the force measurement of these nano-sized particles is missing. We detected that the sizes of LDL and HDL in liquid are close to the commonly known values. The Young's modulus of LDL or HDL is ∼0.4 GPa which is similar to that of some viral capsids or nanovesicles but greatly larger than that of various liposomes. The adhesive force of LDL or HDL is small (∼200 pN). The comparison of AFM detection in air and liquid was also performed which is currently lacking. Our data may provide useful information for better understanding and AFM detection of lipoproteins.

  13. 沉淀法与直接法HDL-c和LDL-c测定研究

    Institute of Scientific and Technical Information of China (English)

    许希红

    2007-01-01

    目的 对直接法和沉淀法测定HDL-c和LDL-c两种测定方法进行比较.方法 采用直接法(聚阴离子多聚物/表面活性剂法)与沉淀法(PTA-Mg2+法、PVS法)对92例随机门诊病人分别进行HDL-c和LDL-c测定.结果 HDL-c测定两种方法无差别;LDL-c测定两种方法差异显著.结论 直接法比沉淀法操作更简便,影响因素少,更适于临床.

  14. Angiopoietin-Like Protein 4 Is a High-Density Lipoprotein (HDL) Component for HDL Metabolism and Function in Nondiabetic Participants and Type-2 Diabetic Patients.

    Science.gov (United States)

    Yang, Long-Yan; Yu, Cai-Guo; Wang, Xu-Hong; Yuan, Sha-Sha; Zhang, Li-Jie; Lang, Jia-Nan; Zhao, Dong; Feng, Ying-Mei

    2017-06-23

    ANGPTL4 (angiopoietin-like protein 4) is a LPL (lipoprotein lipase) inhibitor and is present in high-density lipoprotein (HDL). However, it is not defined whether ANGPTL4 in HDLs could affect HDL metabolism and function in type 2 diabetes mellitus (T2DM). ANGPTL4 levels in the circulation and HDLs were quantified in nondiabetic participants (n=201, 68.7% females) and T2DM patients (n=185, 66.5% females). HDLs were isolated from nondiabetic controls and T2DM patients to assess cholesterol efflux or subjected to endothelial lipase (EL)-overexpressed HEK293 cells for EL hydrolysis in vitro. The association between ANGPTL4 in HDLs and HDL components and function was analyzed in nondiabetic participants or diabetic patients, respectively. Plasma or HDLs of ANGPTL4+/+ and ANGPTL4-/- mice was subjected for cholesterol efflux or EL hydrolysis, respectively. ANGPTL4 levels in the plasma and HDLs were 1.7- and 2.0-fold higher in T2DM patients than nondiabetic controls, respectively (PHDL hydrolysis and dysfunction. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  15. Pre-clinical evaluation of rHDL encapsulated retinoids for the treatment of Neuroblastoma

    Directory of Open Access Journals (Sweden)

    Nirupama eSabnis

    2013-03-01

    Full Text Available Despite major advances in pediatric cancer research, there has been only modest progress in the survival of children with high risk neuroblastoma (HRNB. The long term survival rates of HRNB in the United States are still only 30-50%. Due to resistance that often develops during therapy, development of new effective strategies is essential to improve the survival and overcome the tendency of HRNB patients to relapse subsequent to initial treatment. Current chemotherapy regimens also have a serious limitation due to off target toxicity. In the present work, we evaluated the potential application of reconstituted high density lipoprotein (rHDL containing fenretinide (FR nanoparticles as a novel approach to current neuroblastoma therapeutics. The characterization and stability studies of rHDL-FR nanoparticles showed small size (<40nm and high encapsulation efficiency. The cytotoxicity studies of free FR vs. rHDL/ FR towards the neuroblastoma cell lines SK-N-SH and SMS-KCNR showed 2.8 and 2 fold lower IC50 values for the rHDL encapsulated FR vs. free FR. More importantly, the IC50 value for retinal pigment epithelial cells (ARPE-19, a recipient of off target toxicity during FR therapy, was over 40 times higher for the rHDL/ FR as compared to that of free FR. The overall improvement in in vitro selective therapeutic efficiency was thus about 100 fold upon encapsulation of the drug into the rHDL nanoparticles. These studies support the potential value of this novel drug delivery platform for treating pediatric cancers in general, and neuroblastoma in particular

  16. Oxidative profiles of LDL and HDL isolated from women with preeclampsia.

    Science.gov (United States)

    León-Reyes, G; Maida-Claros, R F; Urrutia-Medina, A X; Jorge-Galarza, E; Guzmán-Grenfell, A M; Fuentes-García, S; Medina-Navarro, R; Moreno-Eutimio, M A; Muñoz-Sánchez, J L; Hicks, J J; Torres-Ramos, Y D

    2017-05-16

    Oxidative stress causes biochemical changes in lipids and proteins; these changes can induce damage to the vascular endothelium and create maternal complications that are characteristic of preeclampsia. In this study, we evaluated the oxidative profile of lipoproteins isolated from women with preeclampsia. Thirty women diagnosed with preeclampsia and thirty women without preeclampsia were included in the study. Lipid-damage biomarkers, including conjugated dienes, lipohydroperoxides and malondialdehyde, were measured. The reduction of nitroblue tetrazolium, the formation of dityrosines, and the carbonylation of proteins were assessed as indicators of protein damage. The protective activity of HDL-c was evaluated by the paraoxonase-I activity present on the HDL-c particles. Serum lipid profiles were also quantified in both groups. Data were analysed using Student's t test and the Pearson correlation coefficient. Our results demonstrated in PE women evident oxidative changes in the lipids and proteins in HDL-c and LDL-c particles and the activity of the antioxidant enzyme PON-I decreased 59.9%. HDL-c exhibited self-defence, as demonstrated by the negative correlation between paraoxonase-I activity and the formation of lipohydroperoxides in HDL-c (r = -0.3755, p HDL-c isolated from women with preeclampsia show oxidative damage to lipids and proteins. We propose an oxidative profile based on the oxidation levels indicated by each of the markers used. We also found that paraoxonase-I is inactivated in the presence of lipohydroperoxides. Antioxidant support might be helpful to reduce oxidative stress in patients with preeclampsia. Further investigations are necessary to define the association between antioxidant activities and preeclampsia.

  17. Markers of Systemic Inflammation and Apo-AI Containing HDL Subpopulations in Women with and without Diabetes

    Directory of Open Access Journals (Sweden)

    Giuseppina T. Russo

    2014-01-01

    Full Text Available Background. Besides their role in reverse cholesterol transport, HDL particles may affect the atherosclerotic process through the modulation of subclinical inflammation. HDL particles differ in size, composition, and, probably, anti-inflammatory properties. This hypothesis has never been explored in diabetic women, frequently having dysfunctional HDL. The potential relationship between lipid profile, Apo-AI containing HDL subclasses distribution, and common inflammatory markers (hsCRP, IL-6 was examined in 160 coronary heart disease- (CHD- free women with and without type 2 diabetes. Results. Compared to controls, diabetic women showed lower levels of the atheroprotective large α-1, α-2, and pre-α-1 and higher concentration of the small, lipid-poor α-3 HDL particles (P<0.05 all; diabetic women also had higher hsCRP and IL-6 serum levels (age- and BMI-adjusted P<0.001. Overall, HDL subclasses significantly correlated with inflammatory markers: hsCRP inversely correlated with α-1 (P=0.01 and pre-α-1 (P=0.003; IL-6 inversely correlated with α-1 (P=0.003, α-2 (P=0.004, and pre-α-1 (P=0.002 and positively with α-3 HDL (P=0.03. Similar correlations were confirmed at univariate regression analysis. Conclusions. More atheroprotective HDL subclasses are associated with lower levels of inflammatory markers, especially in diabetic women. These data suggest that different HDL subclasses may influence CHD risk also through the modulation of inflammation.

  18. Markers of Systemic Inflammation and Apo-AI Containing HDL Subpopulations in Women with and without Diabetes.

    Science.gov (United States)

    Russo, Giuseppina T; Giandalia, Annalisa; Romeo, Elisabetta L; Alibrandi, Angela; Horvath, Katalin V; Asztalos, Bela F; Cucinotta, Domenico

    2014-01-01

    Background. Besides their role in reverse cholesterol transport, HDL particles may affect the atherosclerotic process through the modulation of subclinical inflammation. HDL particles differ in size, composition, and, probably, anti-inflammatory properties. This hypothesis has never been explored in diabetic women, frequently having dysfunctional HDL. The potential relationship between lipid profile, Apo-AI containing HDL subclasses distribution, and common inflammatory markers (hsCRP, IL-6) was examined in 160 coronary heart disease- (CHD-) free women with and without type 2 diabetes. Results. Compared to controls, diabetic women showed lower levels of the atheroprotective large α-1, α-2, and pre-α-1 and higher concentration of the small, lipid-poor α-3 HDL particles (P diabetic women also had higher hsCRP and IL-6 serum levels (age- and BMI-adjusted P HDL subclasses significantly correlated with inflammatory markers: hsCRP inversely correlated with α-1 (P = 0.01) and pre-α-1 (P = 0.003); IL-6 inversely correlated with α-1 (P = 0.003), α-2 (P = 0.004), and pre-α-1 (P = 0.002) and positively with α-3 HDL (P = 0.03). Similar correlations were confirmed at univariate regression analysis. Conclusions. More atheroprotective HDL subclasses are associated with lower levels of inflammatory markers, especially in diabetic women. These data suggest that different HDL subclasses may influence CHD risk also through the modulation of inflammation.

  19. [Lipoproteins HDL and coronary artery disease: a molecular mechanism of fibrate].

    Science.gov (United States)

    Kaletha, Krystian; Chodorowski, Zygmunt; Anand, Izabela Sein; Rybakowska, Iwona; Nagel-Starczynowska, Gabriela

    2003-01-01

    The importance of dyslipidemia in the development of cardiovascular disease is now recognized as a central factor of equal, if not greater significance than any other risk factor. Although correction of high level of low-density lipoproteins (LDL) has been regarded now as the main goal of therapy, it has now been reaffirmed that the contribution of low level of high-density lipoproteins (HDL) to the risk of ischaemic heart disease should also be considered. In the therapy of dislipidemias with hipertriglyceridemia and decreased level of HDL lipoprotein fibrates play an especially important role. In the article the molecular mechanism of fibrates action is presented.

  20. Low HDL levels in sepsis versus trauma patients in intensive care unit.

    Science.gov (United States)

    Tanaka, Sébastien; Labreuche, Julien; Drumez, Elodie; Harrois, Anatole; Hamada, Sophie; Vigué, Bernard; Couret, David; Duranteau, Jacques; Meilhac, Olivier

    2017-12-01

    The protective cardiovascular effect of high-density lipoproteins (HDLs) is considered to chiefly rely on reverse cholesterol transport from peripheral tissues back to the liver. However, HDL particles display pleiotropic properties, including anti-inflammatory, anti-apoptotic or antioxidant functions. Some studies suggest that HDL concentration decreases during sepsis, and an association was reported between low HDL levels and a poor outcome. Like sepsis, trauma is also associated with a systemic inflammatory response syndrome. However, no study has yet explored changes in lipid profiles during trauma. We sought to compare lipid profiles between sepsis and trauma patients in intensive care unit (ICU). In septic patients, we analyzed the association between lipid profile, severity and prognosis. A prospective, observational, single-centered study was conducted in a surgical ICU. For each patient, total cholesterol, HDL, triglyceride and low-density lipoprotein cholesterol levels were assessed at admission. Short-term prognosis outcome was prospectively assessed. Seventy-five consecutive patients were admitted (50 sepsis and 25 trauma). There was no difference in SOFA and SAPSII scores between the two groups. Patients with sepsis had lower total cholesterol levels than patients with trauma. Regarding the lipoprotein profile, only HDLs differed significantly between the two groups (median [IQR] = 0.33 mmol/l [0.17-0.78] in sepsis patients versus median [IQR] = 0.99 mmol/l [0.74-1.28] in trauma patients; P HDL concentration and the length of ICU stay (r = -0.35; P = 0.03) in the group of survivor septic patients at ICU discharge. In addition, poor outcome defined as death or a SOFA score >6 at day 3 was associated with lower HDL levels (median [IQR] = 0.20 mmol/l [0.11-0.41] vs. 0.35 mmol/l [0.19-0.86] in patients with poor outcome versus others; P = 0.03). Lipid profile was totally different between sepsis and trauma in ICU patients: HDL levels were

  1. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus).

    Science.gov (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood

    2013-02-01

    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  2. Characterizing and controlling intrinsic biases of lambda exonuclease in nascent strand sequencing reveals phasing between nucleosomes and G-quadruplex motifs around a subset of human replication origins

    DEFF Research Database (Denmark)

    Foulk, M. S.; Urban, J. M.; Casella, Cinzia;

    2015-01-01

    Nascent strand sequencing (NS-seq) is used to discover DNA replication origins genome-wide, allowing identification of features for their specification. NS-seq depends on the ability of lambda exonuclease (lambda-exo) to efficiently digest parental DNA while leaving RNA-primer protected nascent...... are not general determinants for origin specification but may play a role for a subset. Interestingly, we observed a periodic spacing of G4 motifs and nucleosomes around the peak summits, suggesting that G4s may position nucleosomes at this subset of origins. Finally, we demonstrate that use of Na+ instead of K...

  3. Impact of estimated HDL particle size via the ratio of HDL-C and apoprotein A-I on short-term prognosis of diabetic patients with stable coronary artery disease.

    Science.gov (United States)

    Hong, Li-Feng; Yang, Bo; Luo, Song-Hui; Li, Jian-Jun

    2014-09-01

    Revascularization and statin therapy are routinely used in the management of stable coronary artery disease. However, it is unclear whether the estimated high-density lipoprotein (HDL) particle size (eHDL-S), the ratio of HDL cholesterol (HDL-C) to apoprotein A-I (apoA-I), is associated with the clinical outcomes of diabetic patients with stable coronary artery disease (CAD). We performed a prospective cohort study of 328 patients diagnosed with stable CAD by coronary angiography. Patients were followed up for a mean duration of 12 months. The patients were divided into three groups by the tertiles of eHDL-S: low eHDL-S ( 0.79, n = 99). The associations between the baseline eHDL-S and short-term outcomes were evaluated using the Kaplan-Meier method and Cox proportional regression. The low eHDL-S group had higher triglyceride, hemoglobin A1c, uric acid, and leukocyte count than the other groups. During the follow-up period, 47/328 patients experienced a pre-specified outcome. According to the Kaplan-Meier analysis, the incidence of pre-specified outcomes was lower in the high eHDL-S group (P = 0.04). However, eHDL-S was not independently associated with adverse outcomes in Cox proportional hazards regression (hazard ratio (HR): 0.23, 95% confidence interval (95% CI): 0.01-11.24, P = 0.493). Although the eHDL-S was associated with inflammatory biomarkers, it was not independently associated with the short-term prognosis of diabetic patients with stable CAD in the era of revascularization and potent statin therapy.

  4. Emergent biomarkers of residual cardiovascular risk in patients with low HDL-c and/or high triglycerides and average LDL-c concentrations: focus on HDL subpopulations, Oxidized LDL, adiponectin, and uric acid.

    Science.gov (United States)

    Mascarenhas-Melo, Filipa; Palavra, Filipe; Marado, Daniela; Sereno, José; Teixeira-Lemos, Edite; Freitas, Isabel; Isabel-Mendonça, Maria; Pinto, Rui; Teixeira, Frederico; Reis, Flávio

    2013-01-01

    This study intended to determine the impact of HDL-c and/or TGs levels on patients with average LDL-c concentration, focusing on lipidic, oxidative, inflammatory, and angiogenic profiles. Patients with cardiovascular risk factors (n = 169) were divided into 4 subgroups, combining normal and low HDL-c with normal and high TGs patients. The following data was analyzed: BP, BMI, waist circumference and serum glucose, Total-c, TGs, LDL-c, oxidized-LDL, total HDL-c and HDL subpopulations, paraoxonase-1 (PON1) activity, hsCRP, uric acid, TNF- α , adiponectin, VEGF, and iCAM1. The two populations with increased TGs levels, regardless of the normal or low HDL-c, presented obesity and higher waist circumference, Total-c, LDL-c, Ox-LDL, and uric acid. Adiponectin concentration was significantly lower and VEGF was higher in the population with cumulative low values of HDL-c and high values of TGs, while HDL quality was reduced in the populations with impaired values of HDL-c and/or TGs, viewed by reduced large and increased small HDL subfractions. In conclusion, in a population with cardiovascular risk factors, low HDL-c and/or high TGs concentrations seem to be associated with a poor cardiometabolic profile, despite average LDL-c levels. This condition, often called residual risk, is better evidenced by using both traditional and nontraditional CV biomarkers, including large and small HDL subfractions, Ox-LDL, adiponectin, VEGF, and uric acid.

  5. Buildup of aerosol precursor gases and sulfur-induced activation of soot in nascent jet aircraft exhaust plumes

    Energy Technology Data Exchange (ETDEWEB)

    Kaercher, B.; Hirschberg, M.M.; Fabian, P. [Muenchen Univ. (Germany). Lehrstuhl fuer Bioklimatologie und Immissionsforschung; Gerz, T. [Deutsche Forschungsanstalt fuer Luft- und Raumfahrt e.V. (DLR), Oberpfaffenhofen (Germany). Inst. fuer Physik der Atmosphaere

    1997-12-31

    Research issues concerning the chemical transformation of exhaust trace gases are summarized. The photochemical evolution of NO{sub x} early in the plume is strongly coupled to plume mixing. Substantial amounts of HNO{sub 3} are generated in nascent plumes even if no NO{sub 2} is emitted. The production of H{sub 2}SO{sub 4} becomes very efficient if part of the fuel sulfur is emitted as SO{sub 3}. Each emitted soot particle can acquire 1-10% by mass fully oxidized sulfur molecules prior to binary homogeneous nucleation, if a few percent of the exhaust SO{sub x} are emitted as SO{sub 3}, indicating an important activation pathway for soot, and leading to a marked enhancement of new aerosol formation and growth rates. (author) 11 refs.

  6. POF regulates the expression of genes on the fourth chromosome in Drosophila melanogaster by binding to nascent RNA.

    Science.gov (United States)

    Johansson, Anna-Mia; Stenberg, Per; Allgardsson, Anders; Larsson, Jan

    2012-06-01

    In Drosophila, two chromosome-wide compensatory systems have been characterized: the dosage compensation system that acts on the male X chromosome and the chromosome-specific regulation of genes located on the heterochromatic fourth chromosome. Dosage compensation in Drosophila is accomplished by hypertranscription of the single male X chromosome mediated by the male-specific lethal (MSL) complex. The mechanism of this compensation is suggested to involve enhanced transcriptional elongation mediated by the MSL complex, while the mechanism of compensation mediated by the painting of fourth (POF) protein on the fourth chromosome has remained elusive. Here, we show that POF binds to nascent RNA, and this binding is associated with increased transcription output from chromosome 4. We also show that genes located in heterochromatic regions spend less time in transition from the site of transcription to the nuclear envelope. These results provide useful insights into the means by which genes in heterochromatic regions can overcome the repressive influence of their hostile environment.

  7. Pre-β-HDL formation relates to high-normal free thyroxine in type 2 diabetes mellitus.

    Science.gov (United States)

    van Tienhoven-Wind, Lynnda J N; Perton, Frank G; Dullaart, Robin P F

    2016-01-01

    Low-normal thyroid function within the euthyroid range may influence plasma lipoprotein levels. Associations between variation in thyroid function and pre-β-high density lipoproteins (pre-β-HDL), i.e. lipid-poor or lipid free HDL particles that act as initial acceptor of cell-derived cholesterol, are unknown. We determined relationships of plasma pre-β-HDL with thyroid function in euthyroid subjects with and without type 2 diabetes mellitus (T2DM). TSH, free T4, plasma (apo)lipoproteins, pre-β-HDL, pre-β-HDL formation (pre-β-HDL generation during incubation with lecithin:cholesterol acyltransferase being inhibited) and phospholipid transfer protein (PLTP) activity were measured in fasting plasma from 72 T2DM and 82 non-diabetic subjects. TSH was similar and free T4 was slightly higher (P diabetic subjects. HDL cholesterol and apoA-I were lower, whereas pre-β-HDL (expressed as % of apoA-I), triglycerides and PLTP activity were higher in T2DM (P HDL formation (in apoA-I concentration and in % of apoA-I) was positively related to free T4, PLTP activity, total cholesterol and triglycerides (P HDL formation was positively related to free T4 (in apoA-I concentration: β = 0.278, P = 0.014; in % of apoA-I: β = 0.343, P = 0.003) in T2DM, but not in non-diabetic subjects (both P > 0.30; interaction terms: both P HDL in T2DM.

  8. Plasma HDL-cholesterol and triglycerides, but not LDL-cholesterol, are associated with insulin secretion in non-diabetic subjects.

    Science.gov (United States)

    Natali, Andrea; Baldi, Simona; Bonnet, Fabrice; Petrie, John; Trifirò, Silvia; Tricò, Domenico; Mari, Andrea

    2017-04-01

    Experimental data support the notion that lipoproteins might directly affect beta cell function, however clinical data are sparse and inconsistent. We aimed at verifying whether, independently of major confounders, serum lipids are associated with alterations in insulin secretion or clearance non-diabetic subjects. Cross sectional and observational prospective (3.5yrs), multicentre study in which 1016 non-diabetic volunteers aged 30-60yrs. and with a wide range of BMI (20.0-39.9kg/m(2)) were recruited in a setting of University hospital ambulatory care (RISC study). baseline fasting lipids, fasting and OGTT-induced insulin secretion and clearance (measured by glucose and C-peptide modeling), peripheral insulin sensitivity (by the euglycemic clamp). Lipids and OGTT were repeated in 980 subjects after 3.5years. LDL-cholesterol did not show independent associations with fasting or stimulated insulin secretion or clearance. After accounting for potential confounders, HDL-cholesterol displayed negative and triglycerides positive independent associations with fasting and OGTT insulin secretion; neither with insulin clearance. Low HDL-cholesterol and high triglycerides were associated with an increase in glucose-dependent and a decrease in non-glucose-dependent insulin secretion. Over 3.5years both an HDL-cholesterol decline and a triglycerides rise were associated with an increase in fasting insulin secretion independent of changes in body weight or plasma glucose. LDL-cholesterol does not seem to influence any major determinant of insulin bioavailability while low HDL-cholesterol and high triglycerides might contribute to sustain the abnormalities in insulin secretion that characterize the pre-diabetic state. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol

    Directory of Open Access Journals (Sweden)

    Meisinger Christine

    2008-02-01

    Full Text Available Abstract Background Toll-like receptor 4 (TLR4, the signaling receptor for lipopolysaccharides, is an important member of the innate immunity system. Since several studies have suggested that type 2 diabetes might be associated with changes in the innate immune response, we sought to investigate the association between genetic variants in the TLR4 gene and incident type 2 diabetes. Methods A case-cohort study was conducted in initially healthy, middle-aged subjects from the MONICA/KORA Augsburg studies including 498 individuals with incident type 2 diabetes and 1,569 non-cases. Seven SNPs were systematically selected in the TLR4 gene and haplotypes were reconstructed. Results The effect of TLR4 SNPs on incident type 2 diabetes was modified by the ratio of total cholesterol to high-density lipoprotein cholesterol (TC/HDL-C. In men, four out of seven TLR4 variants showed significant interaction with TC/HDL-C after correction for multiple testing (p -3. However, none of the investigated variants or haplotypes was associated with type 2 diabetes in main effect models without assessment of effect modifications. Conclusion We conclude that minor alleles of several TLR4 variants, although not directly associated with type 2 diabetes might increase the risk for type 2 diabetes in subjects with high TC/HDL-C. Additionally, our results confirm previous studies reporting sex-related dissimilarities in the development of type 2 diabetes.

  10. Design and Verification of AMBA AHBLite protocol using Verilog HDL

    Directory of Open Access Journals (Sweden)

    Sravya Kante

    2016-04-01

    Full Text Available The SOC plan confronts a crevice between generation limit and time to market weights. The outline space develops with changes underway limits as far as measure of time to plan a framework utilizing these abilities. On one hand, shorter product life cycles are forcing an aggressive reduction of the time-to-market, fast simulation capabilities are required for coping with the immense design space that is to be explored; these are specially needed during early stages of the design. This need has driven the improvement of exchange level models, which are theoretical models that have been designed to run much quicker than synthesizable models.The pressure for faster executing models extends especially to the frequently reused communication libraries. AMBA AHB-Lite addresses the requirements of highperformance synthesizable designs. It is a transport interface that provides support to a solitary transport ace and gives elite data transfer capacity.This paper describes the system level modelling of the Advanced HighperformanceBus Lite (AHB-Lite subset of AHB which is a part of the Advanced Microprocessor Bus Architecture(AMBA. It also inc