Plasma levels of PCSK9 and phenotypic variability in familial hypercholesterolemia.

Abstract:

:The extent of hypercholesterolemia varies considerably in patients with familial hypercholesterolemia (FH). We hypothesized that the variability of the FH phenotype might be partly explained by variation in proprotein convertase subtilisin kexin type 9 (PCSK9) activity. Individuals between 18 and 53 years of age who had been tested for a pathogenic LDLR or APOB mutation were eligible. Mutation carriers with a LDL-C level below the 75(th) percentile (called "FH low") were selected, as well as those with LDL-C above the 90(th) percentile (called "FH high"). Relatives who tested negative for the mutation were the "controls." PCSK9 plasma levels were assessed in 267 individuals who did not receive cholesterol-lowering treatment at the time of the study. Mean PCSK9 plasma levels (95% CI) were lower in the FH-low group compared with the FH-high group [152 (137-167) ng/ml vs. 186 (165-207) ng/ml, P = 0.010] and the control group [177 (164-190) ng/ml, P = 0.013]. Mean PCSK9 levels did not statistically differ between the FH-high and control groups (P = 0.50). Plasma PCSK9 levels are positively associated with LDL-C levels in FH patients and might contribute to the phenotypic severity in this disorder. Therefore, the results of pharmaceutical inhibition of PCSK9 in FH patients are eagerly awaited.

journal_name

J Lipid Res

authors

Huijgen R,Fouchier SW,Denoun M,Hutten BA,Vissers MN,Lambert G,Kastelein JJ

doi

10.1194/jlr.P023994

subject

Has Abstract

pub_date

2012-05-01 00:00:00

pages

979-83

issue

5

eissn

0022-2275

issn

1539-7262

pii

jlr.P023994

journal_volume

53

pub_type

杂志文章
  • Effect of p-chlorophenoxyisobutyrate on the antilipolytic action of insulin and insulin binding in isolated adipocytes.

    abstract::The present study was undertaken to investigate the potentiation by p-chlorophenoxyisobutyrate (CPIB) of the antilipolytic effect of insulin in isolated adipocytes from rats fed a (1) sucrose diet, (2) glycerol-lard diet, or (3) chow diet. CPIB supplementation in the diet consistently resulted in decreased serum trigl...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Ip C,Tepperman HM,Tepperman J

    更新日期:1976-01-01 00:00:00

  • Lipolysis of very low density lipoproteins by heparan sulfate proteoglycan-bound lipoprotein lipase.

    abstract::An in vitro assay to study lipolysis of very low density lipoproteins (VLDL) by heparan sulfate proteoglycan (HSPG-bound lipoprotein lipase (LPL) was developed. Optimal conditions for VLDL lipolysis by HSPG-bound LPL were obtained by incubating plastic wells with 0.5 microg HSPG and 1.5 microg LPL, subsequently. Contr...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: de Man FH,de Beer F,van der Laarse A,Smelt AH,Havekes LM

    更新日期:1997-12-01 00:00:00

  • Specific methylation of plasma nonesterified fatty acids in a one-step reaction.

    abstract::Analysis of plasma nonesterified fatty acids (NEFA) by gas-liquid chromatography requires procedures that are both lengthy and cumbersome. A 45-min direct methylation procedure was carried out at 24-29 degrees C on 150 microliter of plasma added with an internal standard in 5.0 ml of methanol-acetyl chloride 50:1 (v/v...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Lepage G,Roy CC

    更新日期:1988-02-01 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

  • Effects of side chain length on ionization behavior and transbilayer transport of unconjugated dihydroxy bile acids: a comparison of nor-chenodeoxycholic acid and chenodeoxycholic acid.

    abstract::13C-NMR spectroscopy was used to examine the effect of side chain length on the ionization properties and transmembrane transport rate of 3 alpha,7 alpha-dihydroxy bile acids. When solubilized in taurocholate micelles, [23-13C]nor-chenodeoxycholic acid (nor-CDCA) had a pKa of 6.1, similar to that of CDCA (pKa 6.2), it...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Ko J,Hamilton JA,Ton-Nu HT,Schteingart CD,Hofmann AF,Small DM

    更新日期:1994-05-01 00:00:00

  • Stimulatory action of cycloheximide on glucose metabolism in the rat epididymal fat pad.

    abstract::The action of cycloheximide on some parameters of glucose and lipid metabolism was studied in vitro in epidiymal fat pads from fasted rats. Incubation of fat pads with cycloheximide (1 mug/ml) for 2 hours resulted in a two-fold increase in glucose uptake, glucose oxidation, incorporation of glucose into lipids, and re...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: García-Sáinz JA,Piña E,Chagoya de Sánchez V

    更新日期:1977-01-01 00:00:00

  • Dietary cholesterol opposes PUFA-mediated repression of the stearoyl-CoA desaturase-1 gene by SREBP-1 independent mechanism.

    abstract::Stearoyl-CoA desaturase (SCD) catalyzes the rate-limiting step in the cellular synthesis of monounsaturated fatty acids, mainly oleate (18:1) and palmitoleate (16:1), which are the major monounsaturated fatty acids of membrane phospholipids, cholesteryl esters, waxes, and triglycerides. The mouse expresses three well-...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.m100433-jlr200

    authors: Kim HJ,Miyazaki M,Ntambi JM

    更新日期:2002-10-01 00:00:00

  • Selective uptake of HDL cholesteryl esters is active in transgenic mice expressing human apolipoprotein A-I.

    abstract::The direct non-endocytotic uptake of cholesteryl esters (CE) from high density lipoprotein (HDL) plays a major role in HDL CE metabolism in rats and rabbits. In vitro evidence indicates it may also play such a role in humans. However, a study in mice (tracing the CE and apoA-I moieties of HDL) concluded that, while se...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Khoo JC,Pittman RC,Rubin EM

    更新日期:1995-03-01 00:00:00

  • Dietary fat and cholesterol and serum cholesterol in the gerbil.

    abstract::Groups of gerbils were fed purified diets containing either 10 or 20% of safflower, olive, or coconut oil. Each diet was fed without cholesterol and with 0.1 and 0.2% of added cholesterol. The animals were bled after 2, 4, and 8 wk for the determination of the level of serum cholesterol. The major factors affecting th...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Hegsted DM,Gallagher A

    更新日期:1967-05-01 00:00:00

  • Blocking gp130 signaling suppresses autotaxin expression in adipocytes and improves insulin sensitivity in diet-induced obesity.

    abstract::Autotaxin (ATX), which is highly expressed and secreted by adipocytes, functions as the key enzyme to generate lysophosphatidic acid (LPA) from lysophosphatidylcholine. Adipose tissue is the main source of circulating ATX that modulates plasma LPA levels. Upregulation of ATX expression in obese patients and mice is cl...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M075655

    authors: Sun S,Wang R,Song J,Guan M,Li N,Zhang X,Zhao Z,Zhang J

    更新日期:2017-11-01 00:00:00

  • Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans.

    abstract::Macrophage infiltration of white adipose tissue (WAT) is implicated in the metabolic complications of obesity. The precipitating event(s) and function(s) of macrophage infiltration into WAT are unknown. We demonstrate that >90% of all macrophages in WAT of obese mice and humans are localized to dead adipocytes, where ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M500294-JLR200

    authors: Cinti S,Mitchell G,Barbatelli G,Murano I,Ceresi E,Faloia E,Wang S,Fortier M,Greenberg AS,Obin MS

    更新日期:2005-11-01 00:00:00

  • Ahmad-Strong synthesis of 8-, 9-, and 10-pentadecynoic acids.

    abstract::Three pentadecynoic acids, with the triple bond in the 8-, 9-, and 10-positions, have been synthesized on a gram scale in over-all yield of 65% by refinements of the five-step Ahmad-Strong method; isolation of intermediates was shown to be unnecessary prior to purification of the acetylenic nitriles by column chromato...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Howton DR,Stein RA

    更新日期:1969-11-01 00:00:00

  • Identification of domains in apoA-I susceptible to proteolysis by mast cell chymase. Implications for HDL function.

    abstract::When stimulated, rat serosal mast cells degranulate and secrete a cytoplasmic neutral protease, chymase. We studied the fragmentation of apolipoprotein (apo) A-I during proteolysis of HDL(3) by chymase, and examined how chymase-dependent proteolysis interfered with the binding of eight murine monoclonal antibodies (Ma...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Lee M,Uboldi P,Giudice D,Catapano AL,Kovanen PT

    更新日期:2000-06-01 00:00:00

  • Uptake of 7-dehydro derivatives of cholesterol, campesterol, and beta-sitosterol by rat erythrocytes, jejunal villus cells, and brush border membranes.

    abstract::We have determined the effect of the side chain on the uptake of sterols from micellar solutions by isolated rat jejunal villus cells, brush border membranes, and erythrocytes. From an equimolar mixture of 7-dehydrosterols, the uptake decreased with an increasing number of carbon atoms at C24 of the sterol side chain ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Child P,Kuksis A

    更新日期:1983-05-01 00:00:00

  • Measurement of LDL-C after treatment with the CETP inhibitor anacetrapib.

    abstract::Estimation of low-density lipoprotein cholesterol (LDL-C) using the Friedewald (FR) formula is often inaccurate when triglycerides are elevated or VLDL particle composition is altered. We hypothesized that LDL-C estimation by the FR formula and other measurement methods might also be inaccurate in individuals treated ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M032615

    authors: Davidson M,Liu SX,Barter P,Brinton EA,Cannon CP,Gotto AM Jr,Leary ET,Shah S,Stepanavage M,Mitchel Y,Dansky HM

    更新日期:2013-02-01 00:00:00

  • Apolipoprotein B(Arg3500----Gln) allele specific polymerase chain reaction: large-scale screening of pooled blood samples.

    abstract::A two-step polymerase chain reaction (PCR) method for the rapid detection of the apolipoprotein B(Arg3500----Gln) mutation in a mixture of pooled blood samples is described. In the first step PCR, a short gene fragment surrounding codon 3500 is amplified. Subsequently the reaction product is subjected to a second ampl...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Ruzicka V,März W,Russ A,Gross W

    更新日期:1992-10-01 00:00:00

  • Uptake of long-chain fatty acid methyl esters by mammalian cells.

    abstract::Albumin-bound long-chain fatty acid methyl esters (ME) were taken up and utilized by Ehrlich ascites tumor cells and slices of rat heart, liver, and kidney. Much more ME than albumin was taken up by the tumor cells, indicating that ME dissociated from the carrier protein during their uptake. 70-80% of the radioactivit...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Kuhl WE,Spector AA

    更新日期:1970-09-01 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

  • Metabolism of cholesterol-enriched chylomicrons. Catabolism of triglyceride by lipoprotein lipase of perfused heart and adipose tissues.

    abstract::The chemical and biochemical properties of cholesterol-enriched and cholesterol-poor chylomicrons from rat lymph have been compared. The enriched particles, prepared from cholesterol-containing lipid dispersions, passed into the duodenum, had four to ten times the cholesteryl ester content of the control chylomicrons ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Fielding CJ,Renston JP,Fielding PE

    更新日期:1978-08-01 00:00:00

  • Plasma free fatty acid transport during prolonged glucose consumption and its relationship to plasma triglyceride fatty acids in man.

    abstract::Plasma free fatty acid (FFA) transport in human subjects has been studied during the course of prolonged ingestion of different amounts of glucose. Compared with the fasting state, hypocaloric glucose intake resulted in marked suppression of net transport of FFA with no change in (fractional) turnover rate. There was ...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Barter PJ,Nestel PJ

    更新日期:1972-07-01 00:00:00

  • Effect of phospholipids on the structure of Triatoma infestans lipophorin studied by fluorescence methods.

    abstract::To study the role of phospholipids in the lipophorin structure, they were removed by phospholipase A2 treatment. Fluorescence lifetimes and accessibility to acrylamide quenching of different diphenylhexatrienyl derivatives, which were used as analogues of the different lipid components, indicate a surface localization...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Rimoldi OJ,Garda HA,Brenner RR

    更新日期:1996-10-01 00:00:00

  • Macrophage-derived factors increase low density lipoprotein uptake and receptor number in cultured human liver cells.

    abstract::Recent evidence suggests the possibility that macrophages can influence lipoprotein metabolism. Therefore we investigated the ability of cultured macrophages to alter low density lipoprotein (LDL) uptake in a human liver cell line (HepG2). Conditioned media from phlogogenic-induced mouse peritoneal macrophages or from...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Grove RI,Mazzucco C,Allegretto N,Kiener PA,Spitalny G,Radka SF,Shoyab M,Antonaccio M,Warr GA

    更新日期:1991-12-01 00:00:00

  • Mechanism of the defect in cholesteryl ester clearance from macrophages of atherosclerosis-susceptible White Carneau pigeons.

    abstract::Recent studies from our laboratory (Yancey, P.G., and R. W. St. Clair. 1992. Arterioscler. Thromb. 12: 1291-1304) have shown that cultured peritoneal macrophages from White Carneau (WC) pigeons clear cholesteryl esters at a slower rate than do macrophages from Show Racer (SR) pigeons (9% per 24 h vs. 42% per 24 h, res...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Yancey PG,St Clair RW

    更新日期:1994-12-01 00:00:00

  • 7α-hydroxy-3-oxo-4-cholestenoic acid in cerebrospinal fluid reflects the integrity of the blood-brain barrier.

    abstract::There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cer...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.P044982

    authors: Saeed A,Floris F,Andersson U,Pikuleva I,Lövgren-Sandblom A,Bjerke M,Paucar M,Wallin A,Svenningsson P,Björkhem I

    更新日期:2014-02-01 00:00:00

  • n-3 PUFA dietary supplementation inhibits proliferation and store-operated calcium influx in thymoma cells growing in Balb/c mice.

    abstract::The antitumor effect of daily individual administration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (2 g/kg body weight) in Balb/c mice bearing a transplantable thymoma was investigated. Mice received oleic acid (control group), EPA and DHA ethyl esters starting 10 days before tumor inoculation. Anal...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Calviello G,Palozza P,Di Nicuolo F,Maggiano N,Bartoli GM

    更新日期:2000-02-01 00:00:00

  • Primary structure of apolipoprotein A-II from inbred mouse strain BALB/c.

    abstract::The primary structure of apolipoprotein A-II (apoA-II) isolated from the plasma high density lipoprotein (HDL) fraction of the inbred mouse strain BALB/c is described in this work. The complete 78 amino acid protein sequence was determined by proteolytic fragmentation, gas-phase microsequence analysis, and fast atom b...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Miller CG,Lee TD,LeBoeuf RC,Shively JE

    更新日期:1987-03-01 00:00:00

  • CLA differently regulates adipogenesis in stromal vascular cells from porcine subcutaneous adipose and skeletal muscle.

    abstract::Conjugated linoleic acid (CLA), a mixture of isomers of linoleic acid, has previously been shown to be able to decrease porcine subcutaneous (SC) adipose tissue levels while increasing the count of intramuscular (IM) adipose tissue in vivo. However, the underlying mechanisms through which it acts are poorly understood...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M600525-JLR200

    authors: Zhou X,Li D,Yin J,Ni J,Dong B,Zhang J,Du M

    更新日期:2007-08-01 00:00:00

  • Triglyceride alters lysosomal cholesterol ester metabolism in cholesteryl ester-laden macrophage foam cells.

    abstract::In late-stage atherosclerosis, much of the cholesterol in macrophage foam cells resides within enlarged lysosomes. Similarly, human macrophages incubated in vitro with modified LDLs contain significant amounts of lysosomal free cholesterol and cholesteryl ester (CE), which disrupts lysosomal function similar to macrop...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M800659-JLR200

    authors: Ullery-Ricewick JC,Cox BE,Griffin EE,Jerome WG

    更新日期:2009-10-01 00:00:00

  • Apolipoprotein A-I assayed in human serum by isotope dilution as a potential standard for immunoassay.

    abstract::We measured the amount of apoA-I in serum by isotope dilution, finding 1.33 mg/ml (standard deviation 0.177) in six normolipidemic, healthy subjects. We developed this method by adapting published techniques to purify apoA-I from 3 ml of serum in two steps: density gradient ultracentrifugation and high performance liq...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:

    authors: Weech PK,Jewer D,Marcel YL

    更新日期:1988-01-01 00:00:00

  • Antiobesity action of epsilon-polylysine, a potent inhibitor of pancreatic lipase.

    abstract::In vitro, -polylysine (EPL) strongly inhibited the hydrolysis of trioleoylglycerol emulsified with phosphatidylcholine (PC) and taurocholate by either pancreatic lipase or carboxylester lipase. The EPL concentration required for 50% inhibition of pancreatic lipase, 0.12 microM, was eight times lower than the concentra...

    journal_title:Journal of lipid research

    pub_type: 杂志文章

    doi:10.1194/jlr.M600168-JLR200

    authors: Tsujita T,Takaichi H,Takaku T,Aoyama S,Hiraki J

    更新日期:2006-08-01 00:00:00