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1.
Lipoprotein-(a) [Lp(a)] is a highly atherogenic lipoprotein with unknown
function, consisting of a low-density lipoprotein (LDL) core and the apo(a)
glycoprotein. The characteristic structural feature of apo(a) is the
presence of multiple so called "kringle' repeats which are in part
identical and in part exhibit slight sequence differences. The assembly of
apo(a) and LDL, which is determinant for plasma Lp(a) levels, takes place
extracellularly and requires specific structural motifs in apo(a) and apoB.
Here we studied the structural features in apo(a) necessary for
high-efficient assembly. Thirteen recombinant apo(a) glycoproteins, which
differed in the set of kringle-IV (K-IV) motifs, were expressed in COS-7
cells and incubated with LDL. The rate of total and disulfide-stabilized
Lp(a) complex formation was measured by an immunochemical assay. Constructs
containing K-IV T(type)5-T10 yielded almost 100% total and 80% stable
complexes, respectively. Deletion or replacement of the different kringles
revealed that K-IV T6 and T7 were responsible for the high-yield assembly
and that K-IV T5 had an amplifying effect. Increasing the absolute number
of K-IV repeats had an additional amplifying effect. The rate of Lp(a)
assembly correlated strongly with the affinity of these constructs to Lys-
Sepharose. Our results have implications for understanding the metabolism
of Lp(a) and may help to design strategies for searching natural apo(a)
mutants with aberrant plasma Lp(a) levels.
相似文献
2.
Lipoprotein(a) [Lp(a)] represents a class of lipoprotein particles having as a protein moiety apoB-100 linked by a single
disulfide bond to apolipoprotein(a) [apo(a)], a multikringle structure with a high degree of homology with plasminogen. A
recognized feature of Lp(a) is its instability on storage caused by attendant protein and lipid modifications that affect
the structural, functional, and immunological properties of this lipoprotein. Here we present data showing that, under appropriate
conditions of cryopreservation, Lp(a) retains the properties of the freshly isolated product, and we provide examples supporting
the stability of this cryopreserved product as a primary standard in immunoassay settings and in cell culture systems. 相似文献
3.
Klaus G. Parhofer Thomas Demant Michael M. Ritter H. Christian Geiss Markus Donner Peter Schwandt 《Lipids》1999,34(4):325-335
Lipoprotein (a) [Lp(a)] is a low-density lipoprotein (LDL) particle with an additional apolipoprotein named apo(a). The concentration
of Lp(a) in plasma is determined to a large extent by the size of the apo(a) isoform. Because elevated Lp(a) concentrations
in plasma are associated with risk for premature coronary heart disease it is important to determine whether variations in
production or catabolism mediate differences in Lp(a) concentration. We determined metabolic parameters of Lp(a) in 17 patients
with heterozygous familial hypercholesterolemia or severe mixed hyperlipidemia by fitting a monoexponential function to the
rebound of Lp(a) plasma concentration following LDL-apheresis. In 8 of those 17 patients this was done twice following two
different aphereses. Although this approach allows one to estimate metabolic parameters without the use of a tracer, it requires
several major assumptions such as that apheresis itself does not change production or catabolism of Lp(a) and that Lp(a) metabolism
can be described by a single compartment. One apheresis decreased Lp(a) concentration by 59.1±8.3%. The fractional catabolic
rate (FCR) was 0.16±0.12 d−1 and production rate 6.27±5.26 mg·kg−1·d−1. However, observed (concentration before first apheresis) and predicted steady-state concentrations differed considerably
(more than 20%) in 9 of 17 patients, indicating that not all assumptions were fulfille in all patients. Production rate but
not FCR was correlated with Lp(a) plasma concentration (r
2=0.43. P=0.004) and molecular weight of apo(a) (r
2=0.48, P=0.011), which confirms radiotracer experiments showing that variations in Lp(a) plasma concentrations are due to differences
in production not catabolism. When parameters were estimated tiwce in a subgroup of eight patients, satisfactory reproducibility
was observed in six patients. Although parameters determined on two occasions correlated well, only FCR was concordant (intraclass
correiation coefficient). Thus, despite the limitations arising from the assumptions implicit to this method, metabolic parameters
of Lp(a) can be estimated from the rebound of plasma concentration following apheresis.
Parts of this study were presented at the meeting of the International Atherosclerosis Society, Paris, October 5–9, 1997. 相似文献
4.
<Emphasis Type="SmallCaps">l</Emphasis>-Carnitine/Simvastatin Reduces Lipoprotein (a) Levels Compared with Simvastatin Monotherapy: A Randomized Double-Blind Placebo-Controlled Study 下载免费PDF全文
M. Florentin M. S. Elisaf C. V. Rizos V. Nikolaou E. Bilianou C. Pitsavos E. N. Liberopoulos 《Lipids》2017,52(1):1-9
Lipoprotein (a) [Lp(a)] is an independent risk factor for cardiovascular disease. There are currently limited therapeutic options to lower Lp(a) levels. l ‐Carnitine has been reported to reduce Lp(a) levels. The aim of this study was to compare the effect of l ‐carnitine/simvastatin co‐administration with that of simvastatin monotherapy on Lp(a) levels in subjects with mixed hyperlipidemia and elevated Lp(a) concentration. Subjects with levels of low‐density lipoprotein cholesterol (LDL‐C) >160 mg/dL, triacylglycerol (TAG) >150 mg/dL and Lp(a) >20 mg/dL were included in this study. Subjects were randomly allocated to receive l ‐carnitine 2 g/day plus simvastatin 20 mg/day (N = 29) or placebo plus simvastatin 20 mg/day (N = 29) for a total of 12 weeks. Lp(a) was significantly reduced in the l ‐carnitine/simvastatin group [?19.4%, from 52 (20–171) to 42 (15–102) mg/dL; p = 0.01], but not in the placebo/simvastatin group [?6.7%, from 56 (26–108) to 52 (27–93) mg/dL, p = NS versus baseline and p = 0.016 for the comparison between groups]. Similar significant reductions in total cholesterol, LDL‐C, apolipoprotein (apo) B and TAG were observed in both groups. Co‐administration of l ‐carnitine with simvastatin was associated with a significant, albeit modest, reduction in Lp(a) compared with simvastatin monotherapy in subjects with mixed hyperlipidemia and elevated baseline Lp(a) levels. 相似文献
5.
Sissel Lund-Katz Yvette M. Murley Errol Yon Kristin L. Gillotte W. Sean Davidson 《Lipids》1996,31(11):1107-1113
High density lipoprotein (HDL) is throught to play a significant role in the process of reverse cholesterol transport. It
has become clear that the apolipoprotein (apo) composition of HDL is important in determining the metabolic fate of this particle.
The major proteins of human HDL are apoAI and APOAII; the latter protein is a disulfide-linked dimer in humans and higher
primates but monomeric in the other species. The consequences of the apo Cys6-Cys6 disulfide bridge in apoAII for human HDL
structure and function are not known. To address this issue, the influence of the Cys6-Cys6 disulfide bridge on the interaction
of human apoAII with palmitoyl-oleoyl phosphatidylcholine has been studied. The size and valence of a series of homogeneous
discoidal complexes containing either monomeric (reduced and carboxymethylated) or dimeric apoAII have been determined, and
their ability to remove cholesterol from rat Fu5AH hepatoma cells grown in culture has been compared. The apoAII dimer and
monomer form discoidal complexes of similar size, with twice as many of the latter molecule required per disc. Removal of
the disulfide bond influences the stability of the helical segments around the edge of the disc as seen by a decrease in α-helix
content of the monomeric protein. The discoidal particles containing the monomeric form of apoAII are somewhat more effective
than particles containing either dimeric apoAII or apoAI in removing cellular cholesterol. Overall, reduction of the disulfide
bridge of apoAII probably does not have a major effect in the determination of HDL particle sizein vivo. It follows that the evolution of the Cys6-Cys6 disulfide bond in higher primates probably has not had a major effect on
the function of the apoAII molecule. 相似文献
6.
The molecular mechanism of vascular pathology mediated by circulating lipoprotein(a) [Lp(a)] remains unknown. We examined the role of two distinguishing features of Lp(a) viz non‐covalent complex formation with a low density lipoprotein (LDL) and heavy glycosylation as determinants of binding of this lipoprotein and its LDL complex to cell‐surface receptors. LDL isolated from the Lp(a):LDL complex, free LDL and oxidized LDL were equally efficient in forming a reconstituted complex with pure Lp(a). Complexed LDL in healthy individuals was equal in oxidation status to free LDL. The number of LDL molecules associated with each Lp(a) molecule (LDL index) in plasma samples increased steadily with Lp(a) size (correlation coefficient r = 0.834). Complex reconstituted from purified plasma Lp(a) and LDL maintained the same LDL index as plasma in accordance with Lp(a) size. Consequently, the percentage of complex‐free Lp(a) in the plasma decreased sharply with Lp(a) size (r = ?0.887). Although O‐glycosylation measured in terms of lectin binding increased with Lp(a) size, the LDL index increased significantly faster than O‐glycosylation among Lp(a) phenotypes of different plasma samples. Complexes with varying stoichiometry existed in the same plasma. Extra LDL complex molecules were not recognized by LDL receptors on human macrophages or rat cardiac fibroblasts indicating attachment to Lp(a) involved LDL receptor‐binding sites. However, unlike free LDL complex LDL could attach through Lp(a) to immobilized form of galectin‐1, a lectin ubiquitous on mammalian cells. Results suggest that phenotype‐dependence of the physiological and pathological functions of Lp(a) may operate through differential LDL‐carrier activity. 相似文献
7.
Rahman M; Jia Z; Gabel BR; Marcovina SM; Koschinsky ML 《Protein engineering, design & selection : PEDS》1998,11(12):1249-1256
A number of studies have provided evidence that lipoprotein(a) [Lp(a)]
assembly is a two-step process in which initial non-covalent interactions
between apolipoprotein(a) [apo(a)] and apolipoproteinB-100 (apoB-100)
precede specific disulfide bond formation. We have designed a construct
encoding apo(a) kringle IV type 9 (KIV9) in which the unpaired cysteine at
position 67 in this kringle is replaced with a tyrosine. The single kringle
was expressed in bacteria and purified to homogeneity from cell
homogenates. The purified derivative (designated KIV9deltaCys) was assessed
for its ability to bind to purified human LDL. This interaction was
detected either by ELISA using immobilized LDL or by column chromatography
in which LDL binding to KIV9deltaCys immobilized on Ni2+-Sepharose was
determined. In both cases, the interaction of KIV9deltaCys and LDL was
observed. Further, we demonstrated that the binding interaction was
sensitive to the addition of amino acids including lysine, the lysine
analogue epsilon- aminocaproic acid, arginine, phenylalanine and proline,
with arginine and lysine having the greatest inhibitory effect. Binding of
KIV9deltaCys to an immobilized apoB peptide spanning residues 3732-3745 of
apoB was also demonstrated by ELISA. As was the case for LDL, this binding
interaction was sensitive to the addition of arginine and lysine. Computer
modeling of KIV9 demonstrated an excellent fit with residues 3732-3738
(PSCKLDF) of the apoB peptide. The modeling predicts the presence of
overlapping lysine and phenylalanine-binding pockets in KIV9 which explains
the inhibitory effects of lysine, arginine and phenylalanine which were
observed in the binding assays. In summary, this study represents the first
demonstration that KIV9 can interact directly with LDL through non-covalent
interactions which may contribute to the first step of Lp(a) formation.
相似文献
8.
We tested the hypothesis that aggregated lipoprotein(a) [Lp(a)] is avidly taken up by macrophages. Lp(a) was isolated by sequential
centrifugations and gel chromatography from a patient with high plasma levels of Lp(a) who was being treated with low density
lipoprotein (LDL)-apheresis. Aggregated Lp(a) was prepared by mixing native Lp(a) with 2.5 mmol/L CaCl2, and 54% of the 125I-Lp(a) aggregated after interacting with CaCl2. The binding and degradation of aggregated Lp(a) in macrophages were 4.6- and 4.7-fold higher than those of native Lp(a),
respectively. An excess amount of LDL did not inhibit either increase. Cholesterol esterification in macrophages was markedly
stimulated by aggregated Lp(a), and macrophages were transformed into foam cells. Cytochalasin B, a phagocytosis inhibitor,
strongly inhibited the degradation and cholesterol esterification (78 and 83%, respectively). These findings suggested that
aggregation may be partially involved in Lp(a) accumulation, thereby contributing to the acceleration of atherosclerosis. 相似文献
9.
Angelo Zinellu Salvatore Sotgia Maria Franca Usai Luca Deiana Ciriaco Carru 《European Journal of Lipid Science and Technology》2006,108(5):444-447
Lipoprotein(a) [Lp(a)] is a recognized risk factor for atherosclerotic cardiovascular disease. It is made of a lipoprotein particle containing apoB100 linked by a single disulfide bridge to apolipoprotein(a), a glycosylated protein with a variable mass. Some authors suggest that oxidative modification could explain the contribution of Lp(a) in the development of atheromatous lesions in a comparable way to low‐density lipoproteins (LDL). Recently, the use of capillary electrophoresis to measure the variations in the relative electrophoretic mobility (REM) of LDL subjected to copper oxidation has been proposed. The aim of this work is to employ this method also to monitor the copper‐induced oxidative modification of Lp(a). Migration of Lp(a) was monitored by absorption at 200 nm in a 50 mmol/L tricine, 100 mmol/L methylglucamine, pH 9.7 run buffer. Contrary to the conventional slab gel methods, our procedure provides a rapid and reproducible means to measure the electrophoretic mobility of Lp(a) (migration time <10 min with a CV% <0.5). 相似文献
10.
Sathanur R. Srinivasan Bhandaru Radhakrishnamurthy Edward R. Dalferes Jr. Gerald S. Berenson 《Lipids》1979,14(6):559-565
Serum α-lipoprotein responses to variations in dietary cholesterol, protein, and carbohydrate were studied in different nonhuman
primate species. Chimpanzee, rhesus, green, patas, squirrel and spider monkeys all showed significant interspecies differences
in serum total cholesterol responses to 1.84 mg/kcal exogenous cholesterol. Dietary cholesterol significantly increased the
α-lipoprotein cholesterol in all species except rhesus and chimpanzee. Among these species, there was no relationship between
the basal serum lipoprotein profile and subsequent lipoprotein responses to dietary cholesterol. Although the level of dietary
protein at 6%, 12%, and 37% of calories had no appreciable main effect on serum total cholesterol in spider monkeys, very
low protein diet (6% of calories) produced a significant elevation in α-lipoprotein cholesterol. Serum α-lipoprotein responses
to exogenous cholesterol (1.84 mg/kcal) was highest for the very low protein diet and lowest for low protein diet (12% of
calories). Diets with high sucrose (76.5% of calories) and low saturated fat (12.5% of calories) containing no added cholesterol
were tested in squirrel and spider monkeys and produced a consistent serum total cholesterol response; the α-lipoprotein response
was significantly higher in squirrel monkeys than in spider monkeys. The above findings have implications in experimentally
induced and comparative atherogenesis.
Presented at the Lipoprotein Symposium AOCS meeting, St. Louis, Missouri, May 1978. 相似文献
11.
M. L. Kashyap L. S. Srivastava B. A. Hynd G. Perisutti D. W. Brady P. Gartside C. J. Glueck 《Lipids》1978,13(12):933-942
The purpose of these studies was (a) to examine the relationship between total plasma triglycerides (TG) and the amount of
apolipoprotein CII (apo CII) in triglyceride rich lipoproteins (TRL), and (b) to determine whether TRL could be enriched with
apo CII in vitro. In 13 patients with primary endogenous hypertriglyceridemia, (log10) total plasma TG correlated inversely with the amount of apo CII per unit very low density lipoprotein (VLDL) protein (r=−0.76;p<0.005)
and VLDL TG (r=−0.75; p<0.005). The potency of VLDL to activate milk lipoprotein lipase (LPL) in hydrolyzing triolein was
studied in vitro. LPL activator potency per unit VLDL protein or VLDL TG correlated inversely with (log10) total plasma TG (r=−0.86 and r=−0.76, respectively; p<0.005). LPL activator potency per nM VLDL apo CII also correlated
inversely with (log10) total plasma TG (r=−0.49; p<0.01). In seven patients with familial type V hyperlipoproteinemia, the average amount of apo
CII in TRL protein was subnormal (5.86±0.62% vs 10.0±0.51% in normal subjects). The higher the (log10) total plasma TG, the lower was the apo CII content in TRL protein (r=−0.93; p<0.01). To determine the factors governing
the distribution of apo CII between lipoproteins and whether TRL could be enriched with apo CII, five approaches were undertaken:
(a)125I apo CII was added to mixtures of VLDL and HDL. The amount of labelled apo CII in VLDL was proportional to the ratio of VLDL
to HDL. (b) TRL from four patients with familial type V hyperlipoproteinemia was incubated with high density lipoprotein (HDL)
from a normal subject. An increase in the TRL/HDL ratio was associated with transfer of apo CII from HDL to TRL and a reciprocal
transfer of non-apo CII protein from TRL to HDL. Net apo CII enrichment of TRL protein was possible below a HDL/TRL protein
ratio of ca. 6 under the experimental conditions. (c) A fixed amount of normal plasma feed of TRL was incubated with different
amounts of TRL from two patients with familial type V hyperlipoproteinemia. The amount of apo CII that transferred from normal
TRL free plasma to the patient’s TRL was proportional to the amount of TRL in the mixture. (d) A doubling and tripling in
the amount of apo CII in TRL was found when apo CII was added directly to TRL from a normal subject and TRL from a patient
with familial type V hyperlipoproteinemia, respectively. (e) When apo CII was added directly to normal plasma and plasma from
a patient with primary type IV hyperlipoproteinemia, the peptide was taken up mainly by VLDL and HDL, indicating enrichment
of these fractions. The distribution of the added apo CII in each lipoprotein fraction resembled the distribution in the native
plasma. TRL was isolated after addition of apo CII to plasma from two patients with familial types IV and V, respectively.
Enrichment of TRL with apo CII was associated with an approximate 1.5-fold increase in the LPL activator potency per unit
TRL protein. These studies suggest that firstly, the amount of apo CII in TRL is inversely related to the severity of hypertriglyceridemia.
Secondly, the distribution of apo CII between TRL and HDL is governed by the mass ratios of these two lipoprotein classes.
Thirdly, plasma TRL and HDL have a reserve binding capacity of apo CII and fourthly, it is possible to enrich these lipoproteins
with this functionally important peptide. Whether net enrichment of TRL with apo CII and also an increase in its biological
activity to activate LPL in vitro is related to increased in vivo catabolic rate requires to be determined. 相似文献
12.
13.
Immunochemical quantification of human plasma Lp(a) lipoprotein 总被引:13,自引:0,他引:13
The Lp(a) lipoprotein was purified from human plasma by ultracentrifugation and gel filtration on 6% agarose. It contained
27% protein, 65% lipid, and 8% carbohydrate. Quantification of the Lp(a) lipoprotein was performed by radial immunodiffusion.
Both within-assay and between-assay coefficients of variation were inversely concentration dependent, decreasing from 20%
and 27%, respectively, at 3 mg/100 ml to 7% and 12%, respectively, at concentrations above 8 mg/100 ml. The lower limit of
sensitivity of the assay was 1.5 mg/100 ml. Of 340 unrelated fasting subjects tested, 81% had levels of the Lp(a) lipoprotein
exceeding this lower limit. The distribution of Lp(a) concentrations in this population was skewed with a mean of 14 mg/100
ml and a median of 8 mg/100 ml. Lp(a) lipoprotein was not significantly correlated with age, sex, or cholesterol or glyceride
concentrations. 相似文献
14.
Most studies on the topic have shown that statin therapy decreases plasma LDL levels but not those of lipoprotein(a) [Lp(a)].
This specificity of action, although previously noted, has not been systematically investigated. In the current study we approached
this problem by monitoring LDL- and Lp(a) cholesterol in 80 hypercholesterolemic subjects with high Lp(a) levels, at entry
and 8 mon after initiation of statin therapy. We found that commonly used direct and indirect LDL cholesterol assays gave
an LDL cholesterol value that comprised both true LDL- and Lp(a) cholesterol. We estimated these two analytes from the values
of Lp(a) protein determined by FLISA and from knowledge of the Lp(a) chemical composition, complemented by data from immunochemical
and ultracentrifugal analyses. Statin therapy, while not affecting plasma Lp(a) protein levels (21.7±10.4, before, and 22.0±10.1
mg/dL, after), caused a decrease in the estimated or true LDL cholesterol (P<0.0001) to values in some cases as low as 10 mg/dL. This drop in true LDL was validated by the decrease in the LDL band in
the ultracentrifugation profiles, and its magnitude was proportional to the degree of total cholesterol lowering and to the
pretreatment true LDL/Lp(a) cholesterol weight ratio. We conclude that true LDL but not Lp(a) cholesterol is affected by statin
therapy and that this specific response cannot be monitored by current LDL cholesterol assays and must, rather, rely on estimates
of these two analytes. 相似文献
15.
Apolipoprotein E (apo E) plays an essential role in lipoprotein metabolism, where it is involved in the clearance of chylomicrons
and very low density lipoproteins. Apart from some rate variants, apo E exists in three common isoforms (E2, E3, and E4).
The different isoforms have not only been associated with different plasma lipid levels but have also been correlated with
certain pathological conditions, such as lipid disorders (dysbetalipoproteinemia, hypercholesterolemia), cardiovascular diseases,
and Alzheimer’s disease. Here we describe a rapid, automated test for the determination of the most frequent polymorphisms
(E2, E3, and E4). This polymerase chain reaction-based test allows the reliable discrimination of all six genotypes. The assay
has been developed especially for the nonspecialized routine clinical laboratory by employing an analyzer and chemistry often
present in this type of laboratory. Because of its low costs and easy handling, the assay can be performed on a daily basis. 相似文献
16.
The abnormal metabolism and distribution of plasma lipoproteins have been associated with atherosclerosis and gallstones.
To better understand the process of cholesterol excretion, a study was designed to determine whether the contribution of lipoprotein
free14C-cholesterol (as LDL or HDL) to biliary cholesterol or primary bile acids differs in two species of nonhuman primates, cebus
and cynomolgus monkeys, having opposite plasma LDL/HDL ratios. Since amino acid conjugation might influence bile acid synthesis
or secretion, the taurine and glycine conjugates of newly synthesized primary bile acids, cholic acid (CA) and chenodeoxycholic
acid (CDCA), were measured in the species capable of conjugating with taurine or glycine (cynomolgus). After total bile acid
pool washout, monkeys were infused with human LDL or HDL labeled with free14C-cholesterol, and the specific activities (SA) of biliary cholesterol and primary bile acid conjugates were determined. In
both species, regardless of the lipoprotein infused, the SA of biliary cholesterol and CA were greater than those for total
bile acids and CDCA, respectively. In cynomolgus, the SA of glycine conjugates was higher for CA than CDCA, while the SA of
taurine conjugates was greater for CDCA than CA. Under these conditions, (i) infused lipoprotein free cholesterol (as either
LDL or HDL) contributed more to biliary cholesterol than to bile acids and more to CA than to CDCA; (ii) glycine conjugated
preferentially with CA rather than CDCA, while taurine was the preferred conjugate for CDCA. Further, whereas the two primary
bile acids had similar rates of synthesis and turnover in cynomolgus, basal bile acid synthesis was much greater in cebus
and the CDCA turnover appeared disproportionately large. 相似文献
17.
Differential Effects of Estrogen and Progestin on Apolipoprotein B100 and B48 Kinetics in Postmenopausal Women 下载免费PDF全文
Stefania Lamon‐Fava Margaret R. Diffenderfer P. Hugh R. Barrett Wing Yee Wan Borbala Postfai Chorthip Nartsupha Gregory G. Dolnikowski Ernst J. Schaefer 《Lipids》2018,53(2):167-175
The distinct effects of the estrogen and progestin components of hormonal therapy on the metabolism of apolipoprotein (apo) B‐containing lipoproteins have not been studied. We enrolled eight healthy postmenopausal women in a placebo‐controlled, randomized, double‐blind crossover study. Each subject received placebo, conjugated equine estrogen (CEE, 0.625 mg/day) and CEE plus medroxyprogesterone acetate (MPA, 2.5 mg/day) for 8 weeks in a randomized order, with a 4‐week washout between phases. Main outcomes were the fractional catabolic rate (FCR) and production rate (PR) of apo B100 in triglyceride‐rich lipoproteins (TRL), intermediate‐density lipoproteins (IDL) and low ‐density lipoprotein (LDL) and of apo B48 in TRL. Compared to placebo, CEE increased TRL apo B100 PR (p = 0.04). CEE also increased LDL apo B100 FCR (p = 0.02), but this effect was offset by a significant increase in LDL apo B100 PR (p = 0.04). Adding MPA to CEE negated the CEE effects resulting in no significant changes in TRL apo B100 PR and LDL apo B100 FCR and PR relative to placebo. Relative to placebo, during CEE there was a trend toward a reduction in plasma apo B48 concentrations and PR (p = 0.07 and p = 0.12, respectively). Compared with CEE, CEE + MPA significantly increased TRL apo B48 FCR (p = 0.02) as well as apo B48 PR (p = 0.01), resulting in no significant changes in apo B48 concentration. Estrogen and progestin have independent and opposing effects on the metabolism of the atherogenic apo B100‐ and apo B48‐containing lipoproteins. 相似文献
18.
Gazi IF Apostolou FA Liberopoulos EN Filippatos TD Tellis CC Elisaf MS Tselepis AD 《Lipids》2011,46(10):953-960
The objective of the present study was to evaluate the effects of acute infection with Leptospira interrogans on lipids, lipoproteins and associated enzymes. Fasting serum levels of total cholesterol (TC), low-density lipoprotein cholesterol
(LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoproteins (apo) A-Ι, B, E, C-II, C-III and
lipoprotein (a) [Lp(a)] were determined in patients with Leptospirosis on diagnosis and 4 months after recovery as well as
in age- and sex-matched controls. Activities of cholesteryl-ester transfer protein (CETP) and lipoprotein-associated phospholipase
A2 (Lp-PLA2) as well as paraoxonase 1 (PON1) hydrolysing activity and levels of cytokines were determined. LDL subclass analysis was
performed with Lipoprint LDL System. Eleven patients (10 men, mean age 49.5 ± 8.4 years) and 11 controls were included. TC,
HDL-C, LDL-C, apoA-I, apoB and Lp(a) levels were lower at baseline, whereas TG and apoE levels were elevated compared with
4 months later. At baseline, higher levels of cytokines and cholesterol concentration of small dense LDL particles (sdLDL-C)
were noticed, whereas LDL particle size was lower compared with follow-up. Activities of plasma Lp-PLA2 and HDL-associated Lp-PLA2 were lower at baseline compared with post treatment values, whereas PON1 activity was similar at baseline and 4 months later.
4 months after recovery, the levels of all lipid parameters evaluated did not differ compared with controls, except for HDL-C
which remained lower. PON1 activity both at baseline and 4 months later was lower in patients compared with controls. Leptospirosis
is associated with atherogenic changes of lipids, lipoproteins and associated enzymes. 相似文献
19.
Plasma kinetic behavior in hyperlipidemic subjects of a lipidic microemulsion that binds to low density lipoprotein receptors 总被引:2,自引:2,他引:2
Raul C. Maranhão Ivete A. Roland Odaly Toffoletto José Antonio Ramires Romélia P. Gonçalves Carlos H. Mesquita Fulvio Pileggi 《Lipids》1997,32(6):627-633
It was previously reported that a protein-free microemulsion (LDE) with structure roughly resembling that of the lipid portion
of low density lipoprotein (LDL) was presumably taken up by LDL receptors when injected into the bloodstream. In contact with
plasma, LDE acquires apolipoproteins (apo) including apo E that would be the ligand for receptor binding. Currently, apo were
associated to LDE by incubation with high density lipoprotein (HDL). LDE-apo uptake by mononuclear cells showed a saturation
kinetics, with an apparent K
m of 13.1 ng protein/mL. LDE-apo is able to displace LDL uptake by mononuclear cells with a K
i of 11.5 ng protein/mL. LDE without apo is, however, unable to displace LDL. The uptake of 14C-HDL is not dislocated by increasing amounts of LDE-apo, indicating that HDL and LDE-apo do not bind to the same receptor
sites. In human hyperlipidemias, LDE labeled with 14C-cholesteryl ester behaved kinetically as expected for native LDL. LDE plasma disappearance curve obtained from eight hypercholesterolemic
patients was markedly slower than that from 10 control normolipidemic subjects [fractional clearance rate (FCR)=0.02±0.01
and 0.12±0.04 h−1, respectively; P<0.0001]. On the other hand, in four severely hypertriglyceridemic patients, LDE FCR was not significantly different from
the controls (0.07±0.03 h−1). These results suggest that LDE can be a useful device to study lipoprotein metabolism. 相似文献
20.
Rahman Mona N.; Petrounevitch Vitali; Jia Zongchao; Koschinsky Marlys L. 《Protein engineering, design & selection : PEDS》2001,14(6):427-438
Elevated plasma concentrations of lipoprotein(a) [Lp(a)] areassociated with an increased risk for the development of atheroscleroticdisease which may be attributable to the ability of Lp(a) toattenuate fibrinolysis. A generally accepted mechanism for thiseffect involves direct competition of Lp(a) with plasminogenfor fibrin(ogen) binding sites thus reducing the efficiencyof plasminogen activation. Efforts to determine the domainsof apolipoprotein(a) [apo(a)] which mediate fibrin(ogen) interactionshave yielded conflicting results. Thus, the purpose of the presentstudy was to determine the ability of single KIV domains ofapo(a) to bind plasmin-treated fibrinogen surfaces as well todetermine their effect on fibrinolysis using an in vitro clotlysis assay. A bacterial expression system was utilized to expressand purify apo(a) KIV
2
, KIV
7
, KIV
9
Cys (which lacks theseventh unpaired cysteine) and KIV
10 which contains a stronglysine binding site. We also expressed and examined three mutantderivatives of KIV
10 to determine the effect of changing criticalresidues in the lysine binding site of this kringle on bothfibrin(ogen) binding and fibrin clot lysis. Our results demonstratethat the strong lysine binding site in apo(a) KIV
10 is capableof mediating interactions with plasmin-modified fibrinogen ina lysine-dependent manner, and that this kringle can increase
in vitro fibrin clot lysis time by ~43% at a concentrationof 10 µM KIV
10
. The ability of the KIV
10 mutant derivativesto bind plasmin-modified fibrinogen correlated with their lysinebinding capacity. Mutation of Trp
70 to Arg abolished bindingto both lysineSepharose and plasmin-modified fibrinogen,while the Trp
70
Phe and Arg
35
Lys substitutions each resultedin decreased binding to these substrates. None of the KIV
10
mutant derivatives appeared to affect fibrinolysis. Apo(a) KIV
7
contains a lysine- and proline-sensitive site capable of mediatingbinding to plasmin-modified fibrinogen, albeit with a lowerapparent affinity than apo(a) KIV
10
. However, apo(a) KIV
7
had no effect on fibrinolysis in vitro
. Apo(a) KIV
2 andKIV
9
Cys did not bind measurably to plasmin-modified fibrinogensurfaces and did not affect fibrinolysis in vitro
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