Effects of ezetimibe and simvastatin on apolipoprotein B metabolism in males with mixed hyperlipidemia.

Abstract:

:Sixteen hyperlipidemic men were enrolled in a randomized, placebo-controlled, double-blind, cross-over study to evaluate the effect of ezetimibe 10 mg and simvastatin 40 mg, coadministered and alone, on the in vivo kinetics of apolipoprotein (apo) B-48 and B-100 in humans. Subjects underwent a primed-constant infusion of a stable isotope in the fed state. The coadministration of simvastatin and ezetimibe significantly reduced plasma concentrations of cholesterol (-43.0%), LDL-C (-53.6%), and triglycerides (-44.0%). Triglyceride-rich lipoproteins (TRL) apoB-48 pool size (PS) was significantly decreased (-48.9%) following combination therapy mainly through a significant reduction in TRL apoB-48 production rate (PR) (-38.0%). The fractional catabolic rate (FCR) of VLDL and LDL apoB-100 were significantly increased with all treatment modalities compared with placebo, leading to a significant reduction in the PS of these fractions. We also observed a positive correlation between changes in TRL apoB-48 PS and changes in TRL apoB-48 PR (r = 0.85; P < 0.0001) with combination therapy. Our results indicate that treatment with simvastatin plus ezetimibe is effective in reducing plasma TRL apoB-48 levels and that this effect is most likely mediated by a reduction in the intestinal secretion of TRL apoB-48. Our study also indicated that the reduction in LDL-C concentration following combination therapy is mainly driven by an increase in FCR of apoB-100 containing lipoproteins.

journal_name

J Lipid Res

authors

Tremblay AJ,Lamarche B,Hogue JC,Couture P

doi

10.1194/jlr.P800061-JLR200

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

1463-71

issue

7

eissn

0022-2275

issn

1539-7262

pii

P800061-JLR200

journal_volume

50

pub_type

临床试验,杂志文章,随机对照试验
  • Characterization of free endogenous C14 and C16 sphingoid bases from Drosophila melanogaster.

    abstract::Sphingolipid metabolites function as signaling molecules in mammalian cells, influencing cell proliferation, migration, and death. Recently, sphingolipid signaling has been implicated in the regulation of developmental processes in Drosophila melanogaster. However, biochemical analysis of endogenous Drosophila sphingo...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M300005-JLR200

    authors: Fyrst H,Herr DR,Harris GL,Saba JD

    更新日期:2004-01-01 00:00:00

  • Effect of repeated apoA-IMilano/POPC infusion on lipids, (apo)lipoproteins, and serum cholesterol efflux capacity in cynomolgus monkeys.

    abstract::MDCO-216, a complex of dimeric recombinant apoA-IMilano (apoA-IM) and palmitoyl-oleoyl-phosphatidylcholine (POPC), was administered to cynomolgus monkeys at 30, 100, and 300 mg/kg every other day for a total of 21 infusions, and effects on lipids, (apo)lipoproteins, and ex-vivo cholesterol efflux capacity were monitor...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M033779

    authors: Kempen HJ,Gomaraschi M,Bellibas SE,Plassmann S,Zerler B,Collins HL,Adelman SJ,Calabresi L,Wijngaard PL

    更新日期:2013-09-01 00:00:00

  • Cholesterol efflux responds to viral load and CD4 counts in HIV+ patients and is dampened in HIV exposed.

    abstract::Cholesterol efflux (CE) capacity has been inversely associated with atherosclerosis and may provide an insight on inflammation occurring in human immunodeficiency virus (HIV) individuals. We address this by studying CE in HIV patients at different stages of HIV disease progression. In this cross-sectional study, CE fr...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M088153

    authors: Tort O,Escribà T,Egaña-Gorroño L,de Lazzari E,Cofan M,Fernandez E,Gatell JM,Martinez E,Garcia F,Arnedo M

    更新日期:2018-11-01 00:00:00

  • Interaction of apolipoprotein A-I in three different conformations with palmitoyl oleoyl phosphatidylcholine vesicles.

    abstract::Interactions of apolipoprotein A-I (apoA-I) with cell membranes appear to be important in the initial steps of reverse cholesterol transport. The objective of this work was to examine the effect of three distinct conformations of apoA-I (lipid-free and in 78 A or 96 A reconstituted high density lipoproteins, rHDL) on ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Tricerri MA,Sanchez SA,Arnulphi C,Durbin DM,Gratton E,Jonas A

    更新日期:2002-02-01 00:00:00

  • Differential uptake of proteoglycan-selected subfractions of low density lipoprotein by human macrophages.

    abstract::Macrophages and arterial chondroitin sulfate proteoglycans (CSPG) are probably associated with extracellular and intracellular lipoprotein deposition during atherogenesis. We found that human arterial CSPG can be used to select subclasses from low density lipoprotein (LDL) with different structural properties and capa...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Hurt-Camejo E,Camejo G,Rosengren B,Lopez F,Wiklund O,Bondjers G

    更新日期:1990-08-01 00:00:00

  • Lipopolysaccharide and tumor necrosis factor cause a fall in plasma concentration of lecithin: cholesterol acyltransferase in cynomolgus monkeys.

    abstract::The effects of intravenous injection of lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNF) were investigated in cynomolgus monkeys (Macaca fascicularis). Injection of 20 micrograms/kg of LPS from E. coli (serotype 055:B5) into cynomolgus monkeys fed a monkey chow diet caused a twofold increase in plasma tr...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Ettinger WH,Miller LD,Albers JJ,Smith TK,Parks JS

    更新日期:1990-06-01 00:00:00

  • Activities of serine palmitoyltransferase (3-ketosphinganine synthase) in microsomes from different rat tissues.

    abstract::Serine palmitoyltransferase [EC 2.3.1.50] catalyzes the first unique reaction of sphingolipid biosynthesis. To determine whether or not different rat tissues are capable of initiating this pathway, its activity was determined for microsomes from rat liver, lung, brain, kidney, intestine, spleen, muscle, heart, pancrea...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Merrill AH Jr,Nixon DW,Williams RD

    更新日期:1985-05-01 00:00:00

  • Combined (n-3 and n-6) essential fatty deficiency is a potent modulator of plasma lipids, lipoprotein composition, and lipolytic enzymes.

    abstract::Essential fatty acids (EFA) are important structural and functional components of cell membranes. Their deficiency has been associated with several clinical and biochemical abnormalities. In the present study, the lipid profile as well as the concentration, composition, and metabolism of lipoproteins were examined in ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Levy E,Thibault L,Garofalo C,Messier M,Lepage G,Ronco N,Roy CC

    更新日期:1990-11-01 00:00:00

  • Improved methodologies for the study of adipose biology: insights gained and opportunities ahead.

    abstract::Adipocyte differentiation and function have become areas of intense focus in the field of energy metabolism; however, understanding the role of specific genes in the establishment and maintenance of fat cell function can be challenging and complex. In this review, we offer practical guidelines for the study of adipocy...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:10.1194/jlr.R046441

    authors: Wang QA,Scherer PE,Gupta RK

    更新日期:2014-04-01 00:00:00

  • Recovery from liver disease in a Niemann-Pick type C mouse model.

    abstract::Loss of function of Niemann-Pick C1 (NPC1) leads to lysosomal free cholesterol storage, resulting in the neurodegenerative disease Niemann-Pick disease type C (NPC). Significant numbers of patients with NPC also suffer from liver disease. Currently, no treatments exist that alter patient outcome, and it is unknown if ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M007211

    authors: Sayre NL,Rimkunas VM,Graham MJ,Crooke RM,Liscum L

    更新日期:2010-08-01 00:00:00

  • Ceramide kinase promotes Ca2+ signaling near IgG-opsonized targets and enhances phagolysosomal fusion in COS-1 cells.

    abstract::Ceramide-1-phosphate (C1P) is a novel bioactive sphingolipid formed by the phosphorylation of ceramide catalyzed by ceramide kinase (CERK). In this study, we evaluated the mechanism by which increased C1P during phagocytosis enhances phagocytosis and phagolysosome formation in COS-1 cells expressing hCERK. Stable tran...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M700442-JLR200

    authors: Hinkovska-Galcheva V,Clark A,VanWay S,Huang JB,Hiraoka M,Abe A,Borofsky M,Kunkel RG,Shanley T,Shayman JA,Lanni F,Petty HR,Boxer LA

    更新日期:2008-03-01 00:00:00

  • Oxidants and antioxidants in atherogenesis. An appraisal.

    abstract::Oxidized low density lipoprotein (Ox-LDL) has a plethora of components that are not present in native LDL. Their presence and quantity depends on the nature, type, and extent of oxidation. Lipids esterified to oxidized fatty acids are the major components formed during the early phase of oxidation and these show a num...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:

    authors: Parthasarathy S,Santanam N,Ramachandran S,Meilhac O

    更新日期:1999-12-01 00:00:00

  • Appraisal of hepatic lipase and lipoprotein lipase activities in mice.

    abstract::A variety of methods are currently used to analyze HL and LPL activities in mice. In search of a simple methodology, we analyzed mouse preheparin and postheparin plasma LPL and HL activities using specific polyclonal antibodies raised in rabbit against rat HL (anti-HL) and in goat against rat LPL (anti-LPL). As an alt...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.D700021-JLR200

    authors: Dallinga-Thie GM,Zonneveld-de Boer AJ,van Vark-van der Zee LC,van Haperen R,van Gent T,Jansen H,De Crom R,van Tol A

    更新日期:2007-12-01 00:00:00

  • Phosphatidyl glycerophosphate phosphatase.

    abstract::An enzyme (phosphatidyl glycerophosphate phosphatase) that catalyzes the formation of phosphatidyl glycerol from phosphatidyl glycerophosphate has been rendered soluble by treatment of the particulate fraction of E. coli with Triton X-100 in the presence of EDTA, and has been partially purified. The enzyme is specific...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Chang YY,Kennedy EP

    更新日期:1967-09-01 00:00:00

  • Scap is required for sterol synthesis and crypt growth in intestinal mucosa.

    abstract::SREBP cleavage-activating protein (Scap) is an endoplasmic reticulum membrane protein required for cleavage and activation of sterol regulatory element-binding proteins (SREBPs), which activate the transcription of genes in sterol and fatty acid biosynthesis. Liver-specific loss of Scap is well tolerated; hepatic synt...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M059709

    authors: McFarlane MR,Cantoria MJ,Linden AG,January BA,Liang G,Engelking LJ

    更新日期:2015-08-01 00:00:00

  • On the structure of cytolipin R, a ceramide tetrahexoside hapten from rat lymphosarcoma.

    abstract::Cytolipin R, a ceramide tetrahexoside isolated from rat lymphosarcoma, was studied by sequential hydrolysis with specific glycosidases which revealed the anomeric configurations of the glycosidic bonds. Sugar linkages were established by combined gas-liquid chromatography and mass spectrometry of the partially methyla...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Laine R,Sweeley CC,Li YT,Kisic A,Rapport MM

    更新日期:1972-07-01 00:00:00

  • Phytanic acid activation in rat liver peroxisomes is catalyzed by long-chain acyl-CoA synthetase.

    abstract::In Refsum disease, disorders of peroxisome biogenesis, and rhizomelic chondrodysplasia punctata, pathological accumulation of phytanic acid results from impaired alpha-oxidation of this branched-chain fatty acid. Previous studies from this laboratory indicated that activation of phytanic acid to its CoA derivative pre...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Watkins PA,Howard AE,Gould SJ,Avigan J,Mihalik SJ

    更新日期:1996-11-01 00:00:00

  • ABCA1 mutants reveal an interdependency between lipid export function, apoA-I binding activity, and Janus kinase 2 activation.

    abstract::ABCA1 exports cholesterol and phospholipids from cells by a multistep pathway that involves forming cell surface lipid domains, solubilizing these lipids by apolipoproteins, binding of apolipoproteins to ABCA1, and activating signaling processes. Here we used a mutational analysis approach to evaluate the relationship...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800366-JLR200

    authors: Vaughan AM,Tang C,Oram JF

    更新日期:2009-02-01 00:00:00

  • Lipid composition of plant mitochondria and of chloroplasts.

    abstract::The mitochondrial lipids from avocado fruit, cauliflower buds, and potato tubers, and the lipids of chloroplasts isolated from avocado fruit and from cauliflower leaves were identified and the concentrations were determined. The lipid composition was compared with that of beef heart mitochondria. Phospholipids constit...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Schwertner HA,Biale JB

    更新日期:1973-03-01 00:00:00

  • Cryo-electron microscopy reveals human low density lipoprotein substructure.

    abstract::In the present study, we have examined the structure of human low density lipoprotein (LDL) using cryo-electron microscopy. Human LDL particles were analyzed in a vitrified frozen-hydrated condition, without chemical fixation or any form of staining. Hence, the lipoproteins were visualized close to their native state....

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Van Antwerpen R,Gilkey JC

    更新日期:1994-12-01 00:00:00

  • Lysophospholipid receptors in vertebrate development, physiology, and pathology.

    abstract::Lysophospholipid (LP) research has experienced a period of renaissance with the discovery of the lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P) receptors in the late 1990s. Vertebrate LP receptors regulate embryogenesis, vascular development, neurogenesis, uterine development, oocyte survival, immune ce...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:10.1194/jlr.R800047-JLR200

    authors: Skoura A,Hla T

    更新日期:2009-04-01 00:00:00

  • Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19.

    abstract::The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein and is phenotypically characterized by fatty liver and elevated plasma triglycerides and VLDL. Recently, these mice have been proposed as an animal model for familial combined hyperlipidemia. The aim of the present study was id...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M400062-JLR200

    authors: Van Greevenbroek MM,Vermeulen VM,De Bruin TW

    更新日期:2004-06-01 00:00:00

  • Structural features of synthetic peptides of apolipoprotein E that bind the LDL receptor.

    abstract::Apolipoprotein (apo) E, via its receptor binding domain contained in residues 140-150, mediates hepatic and peripheral tissue binding of cholesterol-rich lipoproteins. Previously, we reported that a synthetic peptide representing a linear tandem repeat of amino acids 141-155, the 141-155 dimer, binds the low density l...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Dyer CA,Cistola DP,Parry GC,Curtiss LK

    更新日期:1995-01-01 00:00:00

  • Rapid determination by centrifugal ultrafiltration of inter-mixed micellar/vesicular (non-lecithin-associated) bile salt concentrations in model bile: influence of Donnan equilibrium effects.

    abstract::We have developed the technique of rapid (< 2 h) centrifugal ultrafiltration to measure the inter-mixed micellar/vesicular (non-lecithin-associated) bile salt (BS) concentrations (IMC) of individual BS in model biles. This methodology uses a centrifugal concentrator with a reinforced membrane, through which a small fr...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Donovan JM,Jackson AA

    更新日期:1993-07-01 00:00:00

  • Thematic review series: skin lipids. Sebaceous gland lipids: friend or foe?

    abstract::Sebaceous glands are intriguing glands that are found throughout the human body except on the palms of the hands and soles of the feet. The true function of these glands has yet to be determined, but there are several theories, including antioxidant effects, antibacterial effects, and transport of pheromones. Sebaceou...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:10.1194/jlr.R700015-JLR200

    authors: Smith KR,Thiboutot DM

    更新日期:2008-02-01 00:00:00

  • Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review.

    abstract::Epidemiological studies in Greenland Eskimos led to the hypothesis that marine oils rich in n-3 fatty acids (also referred to as omega (omega)-3 fatty acids) are hypolipidemic and ultimately antiatherogenic. Metabolically controlled trials in which large amounts of fish oil were fed to normal volunteers and hyperlipid...

    journal_title:Journal of lipid research

    pub_type: 杂志文章,评审

    doi:

    authors: Harris WS

    更新日期:1989-06-01 00:00:00

  • Alterations of VLDL composition during alimentary lipemia.

    abstract::Apoliprotein (apo) B-100-containing very low density lipoprotein (VLDL) particles secreted from the liver accumulate in plasma during alimentary lipemia. To determine whether changes of VLDL composition occur in the postprandial state that may render these lipoproteins more atherogenic, apoE, C-I, C-II, and C-III, and...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Björkegren J,Hamsten A,Milne RW,Karpe F

    更新日期:1997-02-01 00:00:00

  • Selective incorporation of various C-22 polyunsaturated fatty acids in Ehrlich ascites tumor cells.

    abstract::Three 14C-labeled 22-carbon polyunsaturated fatty acids, 7,10,13,16-[14C]docosatetraenoic acid (22:4(n-6)), 7,10,13,16,19-[14C]docosapentaenoic acid (22:5(n-3)), and 4,7,10,13,16,19-[14C]docosahexaenoic acid (22:6(n-3)), were compared with [3H]arachidonic acid (20:4(n-6] and [14C]linoleic acid (18:2(n-6)) to character...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Masuzawa Y,Okano S,Waku K,Sprecher H,Lands WE

    更新日期:1986-11-01 00:00:00

  • Plasma phospholipid transfer activity is essential for increased atherogenesis in PLTP transgenic mice: a mutation-inactivation study.

    abstract::Plasma phospholipid transfer protein (PLTP) interacts with HDL particles and facilitates the transfer of phospholipids from triglyceride (TG)-rich lipoproteins to HDL. Overexpressing human PLTP in mice increases the susceptibility to atherosclerosis. In human plasma, high-active and low-active forms of PLTP exist. To ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800080-JLR200

    authors: Samyn H,Moerland M,van Gent T,van Haperen R,Metso J,Grosveld F,Jauhiainen M,van Tol A,de Crom R

    更新日期:2008-12-01 00:00:00

  • Hormonal regulation of the cholesterol 7 alpha-hydroxylase gene (CYP7).

    abstract::The transcriptional regulation of the rat cholesterol 7 alpha-hydroxylase gene (CYP7) by hormones and signal transduction pathways was studied by transient transfection assay of the promoter activity. HepG2 cells were transfected with deletion mutants of the CYP7 upstream region linked to the luciferase reporter gene....

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Crestani M,Stroup D,Chiang JY

    更新日期:1995-11-01 00:00:00