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 Resjournal_title
Journal of lipid researchauthors
Huijgen R,Fouchier SW,Denoun M,Hutten BA,Vissers MN,Lambert G,Kastelein JJdoi
10.1194/jlr.P023994subject
Has Abstractpub_date
2012-05-01 00:00:00pages
979-83issue
5eissn
0022-2275issn
1539-7262pii
jlr.P023994journal_volume
53pub_type
杂志文章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:
更新日期:1976-01-01 00:00:00
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:
更新日期:1997-12-01 00:00:00
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:
更新日期:1988-02-01 00:00:00
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:
更新日期:1997-02-01 00:00:00
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:
更新日期:1994-05-01 00:00:00
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:
更新日期:1977-01-01 00:00:00
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
更新日期:2002-10-01 00:00:00
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:
更新日期:1995-03-01 00:00:00
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:
更新日期:1967-05-01 00:00:00
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
更新日期:2017-11-01 00:00:00
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
更新日期:2005-11-01 00:00:00
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:
更新日期:1969-11-01 00:00:00
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:
更新日期:2000-06-01 00:00:00
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:
更新日期:1983-05-01 00:00:00
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
更新日期:2013-02-01 00:00:00
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:
更新日期:1992-10-01 00:00:00
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:
更新日期:1970-09-01 00:00:00
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
更新日期:2004-06-01 00:00:00
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:
更新日期:1978-08-01 00:00:00
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:
更新日期:1972-07-01 00:00:00
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:
更新日期:1996-10-01 00:00:00
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:
更新日期:1991-12-01 00:00:00
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:
更新日期:1994-12-01 00:00:00
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
更新日期:2014-02-01 00:00:00
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:
更新日期:2000-02-01 00:00:00
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:
更新日期:1987-03-01 00:00:00
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
更新日期:2007-08-01 00:00:00
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
更新日期:2009-10-01 00:00:00
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:
更新日期:1988-01-01 00:00:00
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
更新日期:2006-08-01 00:00:00