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Biomedical subjects

H Mezdour

Publications and source records attributed to H Mezdour.

16 recordsLinked to original sources
PubMed1997

Hepatic lipase deficiency increases plasma cholesterol but reduces susceptibility to atherosclerosis in apolipoprotein E-deficient mice.

The effect of hepatic lipase (HL) deficiency on the susceptibility to atherosclerosis was tested using mice with combined deficiencies in HL and apoE. Mice lacking both HL and apoE (hhee) have a plasma total cholesterol of 917 +/- 252 mg/dl (n = 24), which is 184% that of mice lacking only apoE (HHee; 497 +/- 161 mg/dl, n = 20, p < 0. 001). The increase in cholesterol was mainly in beta-migrating very low density lipoproteins, although high density lipoprotein cholesterol (HDLc) was also increased (53 +/- 37 versus 20 +/- 13 mg/dl, p < 0.01). Despite the increase in plasma cholesterol, we found that HL deficiency significantly decreased aortic plaque sizes in female mice fed normal chow (31 x 10(3) +/- 22 x 10(3) microm2 in hhee versus 115 x 10(3) +/- 69 x 10(3) microm2 in HHee, p < 0.001). Reduction of plaque sizes was also observed in female heterozygous apoE-deficient mice fed an atherogenic diet (2 x 10(3) +/- 2.5 x 10(3) microm2 in hhEe versus 56 x 10(3) +/- 49 x 10(3) microm2 in HHEe, p < 0.01). Changes in aortic lesion size were not apparent in the small number of male mice studied. In HHee females, both HDLc and the capacity of high density lipoprotein (HDL) particles to promote cholesterol efflux from cultured cells were 26% of the wild type. The absence of HL in hhee females partially restored HDLc levels to 57% and cholesterol efflux to 55% of the wild type. Circulating pre-beta1-migrating HDL were present in all mutants, suggesting that there are alternative pathways in the formation of these pre-beta-HDL not involving apoE, HL, or cholesteryl ester transfer protein. The improved capacity to promote cholesterol efflux, together with increased HDL, may explain why these animals can overcome the increase in atherogenic lipoproteins.

Animals↗
PubMed1996

Neutral-lipid transfers and cholesteryl ester transfer protein in hemodialyzed patients.

Abnormalities in cholesteryl ester transfers may play a role in the development of atherosclerosis observed in patients with end-stage renal failure treated by chronic hemodialysis. Net neutral-lipid transfers and cholesteryl ester transfer protein activity and mass were investigated in 20 hemodialyzed patients, arbitrarily divided into two groups based on fasting triglyceride levels, and compared to triglyceride-matched control groups. In the hypertriglyceridemic subjects (plasma triglyceride values > 150 mg/dl), high-density lipoprotein cholesterol was decreased, and the net cholesteryl ester transfer rates were significantly higher than the rates in normolipidemic subjects. The comparison of subjects matched for plasma triglyceride and cholesterol levels showed no significant difference in cholesteryl ester or triglyceride transfer rates between patients and controls. Our results suggest that normal or elevated net neutral-lipid transfers are not related to the renal status of the subjects, but rather to their plasma triglyceride levels.

Aged↗
PubMed1995

Genetic but not diet-induced hypercholesterolemia causes low apolipoprotein A-IV level in rabbit sera.

The present report describes a competitive enzyme immunoassay for rabbit apolipoprotein A-IV (apo A-IV). This assay was applied to the determination of its concentration and distribution in sera from normolipidemic and hyperlipidemic rabbits. The assay was sufficiently sensitive to study this 42-kDa protein in lipoproteins fractionated from 200 microliters of serum by FPLC gel filtration. In normolipidemic sera (n = 8), apo A-IV concentration was 5.32 +/- 0.76 mg/dl. A diet rich in cholesterol (0.5%), which induced an 18-fold increase in serum cholesterol, did not significantly alter apo A-IV concentration (6.65 +/- 1.52 mg/dl, n = 8). By contrast, genetically induced hypercholesterolemia (Watanabe heritable hyperlipidemia, WHHL mutation) caused a significantly reduced level of apo A-IV (3.8 +/- 1.14 mg/dl, n = 7). In each of the groups studied, apo A-IV was distributed in two distinct pools; a high-density lipoprotein-(HDL) associated pool and a lipoprotein-free pool. However, compared to normal, the distribution of apo A-IV in WHHL rabbit sera was shifted towards the lipoprotein-free pool. Consistent with previously reported observations on apo A-I, these results are compatible with the hypothesis of an impaired reverse transport of cholesterol in WHHL rabbits, an animal model for familial hypercholesterolemia.

Amino Acid Sequence↗
PubMed1995

Exogenous supply of artificial lipoproteins does not decrease susceptibility to atherosclerosis in cholesterol-fed rabbits.

We investigated the effects of reconstituted apo A-I-containing high-density lipoprotein (r-HDL, homologous to small pre-beta-migrating HDL) and reconstituted triglyceride-rich lipoprotein (r-TRL, a mixture of Intralipid and apo E) on atherogenesis in rabbits fed a 0.5% cholesterol diet for 8 weeks. Male Japanese white rabbits (n = 17) were divided into three groups: the control group (n = 7) received a placebo and 2.5 ml of Intralipid 20 h later; the second group (n = 6) received r-HDL containing 18 mg of apo A-I followed by 2.5 ml of Intralipid; and the third group (n = 4) received 18 mg of r-HDL and 2.5 ml of r-TRL containing 4 mg of apo E. Rabbits were injected with the agents weekly and the same interval (20 h) was maintained between the two injections. Three minutes after the injection of r-HDL, a sharp increase in the pre-beta-migrating fraction was observed. The cholesterol-rich diet similarly increased serum lipids in the three groups. No significant changes of the HDL cholesterol and apo A-I concentrations were observed in the three groups. Conversely, there was a 12-fold increase of apo E which correlated positively with the total cholesterol level. Injection of r-HDL and r-TRL caused slight inhibition of fatty streak development and lipid deposition in the aortic wall, but neither change was statistically significant. Lipid accumulation in the liver was similar in all three groups. These results suggest that the physiological properties of artificial and native lipoproteins may differ.

Animals↗
PubMed1994

Two-site enzyme immunoassay of cholesteryl ester transfer protein with monoclonal and oligoclonal antibodies.

We developed a sandwich-type enzyme immunoassay to measure cholesteryl ester transfer protein (CETP) mass in human plasma. A specific monoclonal antibody (TP-4) that recognizes an epitope located in the C-terminal domain was used for antigen capture and an anti-CETP peptide antibody directed against the 290-306 residue was used for detection. Bound antibodies were revealed with an antibody-peroxidase conjugate specific for rabbit IgG. The presence of 10 mL/L Triton X-100 in the incubation buffer increased antigen exposure of CETP in plasma. The curves for CETP in standard plasma and partially purified CETP were parallel. This technique is rapid (results within 6 h), accurate, precise (mean intra- and interassay CVs 3.6% and 8.4%, respectively), and simple to perform. Assay sensitivity is at microgram concentrations, with a working range of 20-200 micrograms/L. In 40 normolipidemic healthy subjects, the mean CETP concentration in plasma was 1.1 +/- 0.4 mg/L. A strong correlation between CETP concentration and CETP activity (r = 0.91, n = 42) was observed. In plasma, the bulk of CETP was found in high-density lipoprotein fractions. Therefore, this assay may be a useful tool for investigations of CETP and its significance in relevant diseases.

Antibodies↗
PubMed1994

[Transfer of plasma cholesterol and atherosclerosis].

Transfer processes in plasma are determinant in cholesterol metabolism. In many species, including man, there is an alternative route for the disposal of cholesteryl esters (CE) in HDL via transfer to VLDL in exchange for triglycerides (TG), a process dependent on a hydrophobic 74 kDa glycoprotein called cholesteryl ester transfer protein (CETP). In vivo, cholesteryl esters transferred from HDL will contribute to LDL, to which VLDL is converted. Although the prevention of CE accumulation in HDL may enhance the ability of HDL to take up more cholesterol from tissues, high rates of transfer may also increase the risk for atheroma by increasing formation of atherogenic lipoproteins. Conversely, CE retained within HDL, if returned directly to the liver, would be expected to be beneficial. Moreover, in most conditions predisposing to atheroma, CETP activity is raised; whereas species with low or absent CETP activity are at low risk for atherosclerosis.

Animals↗
PubMed1993

[The pharmacological effects of certain compounds on lipoprotein(a)].

Lipoprotein(a) represents a cholesterol ester, LDL-like particle with apo B-100 linked to apo (a). Lp(a) is a fascinating subject of research because of its presumed association with atherosclerotic cardiovascular disease. The reported results do not encourage optimism. Drugs like niacin or fibrates when used alone have been attended by mixed results. Neither clofibrate nor bezafibrate, which reduce the VLDL concentration, affect LP(a) levels. Neither the ion-exchange resin cholestyramine, nor the HMG CoA reductase inhibitor lovastatin reduce the serum concentration of Lp(a). But, we must keep in mind that drugs used to lower plasma Lp(a) levels were designed for apo B and not apo B-apo(a) containing particles. Thus, it may be necessary to develop drugs specifically targeted to Lp(a).

Arteriosclerosis↗
PubMed1992

Concentration and distribution of apolipoproteins A-I and E in normolipidemic, WHHL and diet-induced hyperlipidemic rabbit sera.

Two sandwich-type enzyme immunoassays have been developed to measure apolipoproteins A-I and E in rabbit serum. Specific goat antibodies were purified by affinity chromatography and used both for coating and for preparing antibody-peroxydase conjugates. The sensitivity of these assays is sufficient to allow studies of apo A-I and E distribution in lipoproteins fractionated by gel filtration from 50 microliters of serum. In WHHL rabbits, apo A-I is 5-fold lower (5.2 +/- 2.5 mg/dl) and apo E is 8-fold higher (9.9 +/- 3.5 mg/dl) than in normolipidemic rabbits (29 +/- 4.3 mg/dl and 1.3 +/- 0.5 mg/dl, respectively). In hyperlipidemic rabbits, fed 2 months on a 0.5% cholesterol diet, the apo A-I level was similar (32 +/- 12 mg/dl) to that of normolipidemic rabbits, but the apo E level is 12-fold higher (15.1 +/- 5.5 mg/dl). In addition, HDL particles were enriched with cholesterol and apo E. The bulk of apo E and cholesterol is located in large beta-VLDL in diet-induced hyperlipidemia, whereas they are mainly located in smaller size beta-VLDL in WHHL rabbits. In normolipidemic rabbits apo E occurs mainly in HDL, and cholesterol is distributed in the main three lipoprotein fractions VLDL, LDL and HDL. Interestingly, HDL of WHHL rabbit are deficient in apo A-I. These results are compatible with profound perturbations of lipoprotein composition and metabolism in atherogenic hyperlipidemia.

Animals↗
PubMed1990

Differential electroimmunoassay of human LpA-I lipoprotein particles on ready-to-use plates.

We describe a method for directly measuring LpA-I lipoprotein particles containing apolipoprotein A-I (apo A-I) not associated with apolipoprotein A-II (apo A-II), by differential electroimmunoassay of plasma on ready-to-use plates. Lipoprotein particles containing both apo A-I and apo A-II (LpA-I:A-II) are retained close to the wells when a very high excess of anti-apo A-II is used as compared with anti-apo A-I, whereas the LpA-I particles migrate and react with anti-apo A-I. The method is specific, rapid, and precise. Within- and between-run CVs at three concentrations (high, medium, and low) ranged between 1.51% and 2.72% and 3.01% and 4.56%, respectively. Analytical recovery of isolated LpA-I was from 93% to 115%. Results correlate well with those obtained by two-phase electroimmunoassay, enzyme-linked differential-antibody immunosorbent assay, and immunoaffinity chromatography coupled to enzyme-linked immunosorbent assay. The average normolipidemic concentration of LpA-I was 600 mg/L in 45 women and 490 mg/L in 40 men (P less than 0.0001).

Adult↗
PubMed1990

[Lipoprotein (a). An additional marker of atherosclerosis].

Lipoprotein Lp(a) is a plasma lipoprotein which possesses many similarities to low density lipoprotein (LDL) in its physical and chemical properties. The major protein constituent of both lipoproteins is apolipoprotein B100 (apo B100); however, Lp(a) is unique in that it contains an additional distinct antigen, the (a)-antigen, attached to apo B100 by one or more disulphide bridges. The (a)-glycoprotein has recently been shown to have a striking amino-acid sequence homology with plasminogen; so, Lp(a) seems to be a potential bridge between the fields of atherosclerosis and thrombosis. Metabolic studies have made it clear that Lp(a) is not a product derived from other apo B-containing lipoproteins, but is secreted by the liver as a distinct mature lipoprotein. Although a relationship between elevated serum Lp(a) levels and the occurrence of atherosclerotic diseases had been postulated by several investigators, little is known today about the role of this lipoprotein and/or the mechanism whereby it might predispose to atheroma. However, the new knowledge on the structure of Lp(a) being more and more rapidly acquired, should facilitate the understanding of the mechanism of its atherogenicity and its physiopathological role.

Animals↗
PubMed1989

A selective bi-site immunoenzymatic procedure for human Lp[a] lipoprotein quantification using monoclonal antibodies against apo[a] and apoB.

A selective bi-site ELISA assay procedure for quantification of Lp[a] lipoprotein in human plasma based on linkage of apo[a] to apoB is described. The lipoproteins referred to as apo[a]:B were captured by a mixture of two anti-apo[a] monoclonal antibodies (K07, K09) and were revealed by a mixture of six anti-apoB monoclonal antibodies coupled to peroxidase. Since apo[a] and plasminogen have striking similarities in protein structure, the selective binding of Lp[a]:B in our assay depended upon the marked difference in affinity of the K07 and K09 mixture for Lp[a]:B (Kd = 0.32 x 10(-10) M) versus plasminogen (Kd = 0.47 x 10(-7)M). The high sensitivity (the Lp[a]:B working range 0.06-0.40 micrograms/ml) and the use of anti-apoB as antibody tracer added to the selectivity of the assay. The expression of K07 and K09 epitopes determined by competitive inhibition method and the reactivity of Lp[a]:B particles measured by bi-site ELISA were similar on individual lipoproteins, independent to their plasma levels. The assay is precise, and intra- and interassay coefficients of variation were 4.7% and 9.6%, respectively. It yields quantitative Lp[a]:B values that correlate highly with Lp[a] levels obtained by electroimmunoassay with polyclonal antibody (r = 0.73) or with Lp[a] levels measured by the other bi-site ELISA using only K07 and K09 antibodies (r = 0.96). However, upon analyzing each individual plasma with an arbitrary Lp[a]-cut off of 15 mg/dl, evidence of the qualitative aspect of the lipoprotein was obtained. The group with Lp[a] less than 15 mg/dl had higher frequency of subjects (65%) with the ratio Lp[a]/Lp[a]:B above 1.5.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1988

Antibodies of predetermined specificity to apolipoprotein C-II elicited with a synthetic peptide. Characterization and use for immunoassays.

Antibodies of predetermined specificity raised against a synthetic peptide corresponding to the C-terminal region of apolipoprotein C-II (Apo C-II) 63-79 were shown to be specific for the apolipoprotein by Western blot. The recognition by these antibodies of Apo C-II containing lipoprotein particles (both isolated and in plasma) was studied in a fluid-phase radioimmunoassay and the affinity constant for plasma was determined. The role of lipids in the expression of epitopes was studied by comparing the antigenicity of intact and delipidated Apo C-II containing fractions. The antibodies proved to be as suitable as conventional anti-protein antibodies in an immunoenzymometric assay and, moreover, were able to develop 'rockets' in an electroimmunoassay.

Antibodies↗
PubMed1988

Interaction of LDL, Lp[a], and reduced Lp[a] with monoclonal antibodies against apoB.

Five monoclonal antibodies (2A, 9A, 6B, L3, L7) produced in mice against human apolipoprotein B were investigated by competitive and inhibitive electroimmunoassay (EIA) for their reactivity with low density lipoprotein (LDL), lipoprotein[a] (Lp[a]), and reduced Lp[a]. All of the antibodies reacted with apoB of the different lipoproteins indicated by very similar slopes of the binding curves. None of them gave a positive reaction with apolipoprotein[a]. The amount of apoB required for 50% inhibition of antibody binding varied for the different antibodies and lipoproteins. Antibody 9A showed almost the same affinity for LDL, Lp[a], and reduced Lp[a]. Antibodies 2A and 6B bound about twofold better to LDL and reduced Lp[a] than to untreated Lp[a]. Antibodies L3 and L7 needed nearly threefold higher amounts of Lp[a]-apoB for 50% inhibition of antibody binding than of apoB of LDL and reduced Lp[a]. The amount of apoB required for 50% inhibition of antibody binding was somewhat higher in inhibitive assay than in competitive assay. We suggest that apo[a] covers certain epitopes of apoB in native Lp[a] leading to a reduced reaction with the monoclonal antibodies. However, it could also be that the binding of the [a]antigen to apoB via disulfide bridges causes profound conformational changes of the apoB region exposed to the surface.

Adolescent↗
PubMed1987

Anion-exchange fast protein liquid chromatographic characterization and purification of apolipoproteins A-I, A-II, C-I, C-II, C-III0, C-III1, C-III2 and E from human plasma.

This paper describes a procedure for the rapid isolation of urea-soluble apolipoproteins (apo) from delipidated human very-low- and high-density lipoproteins using anion-exchange fast protein liquid chromatography. The separation was complete within 30 min and peaks corresponding to apolipoproteins A-I, A-II, C-I, C-II, C-III0, C-III1, C-III2 and E were identified by comparing their chromatographic, electrophoretic and immunological behaviour with that of purified standards of each protein. A second purification step is necessary to obtain pure apolipoproteins. Apo E, which is difficult to purify by conventional chromatography, has been obtained in a good yield. The apo C-II that was obtained produced a symmetrical peak on chromatography but three bands in isoelectric focusing. The method can be upgraded to a preparative scale and offers the possibility of direct purification of apolipoproteins both from high-density lipoproteins and (following preliminary gel chromatography) from very-low-density lipoproteins.

Anions↗
PubMed1987

Standardization of an enzymometric assay for apolipoprotein A-I by using mixtures of monoclonal antibodies).

For the standardization of human plasma apolipoprotein A-I assay two well characterized monoclonal antibody mixtures were used to develop a sandwich immunoenzymometric assay. The monoclonal antibody mixture 1 (A05-A17-A30) in solid phase technique was selected on the basis of its higher binding capacity of [125I]HDL (41 ng per well) compared to polyclonal antibody (23 ng per well). The epitopes recognized by monoclonal antibody mixture 1 are surface antigenic sites of apolipoprotein A-I expressed on native HDL as determined by competitive inhibition of labeled HDL. The peroxidase conjugated monoclonal antibody mixture 2 (A03-A05-A17-A51) was selected on the basis of its ability to bind to apolipoprotein A-I captured by monoclonal antibody mixture 1. For this, we used the 125I-labeled monoclonal antibodies. Under optimized assay conditions, the immunoenzymometric assay is precise (intra- and inter-assay coefficients of variations 5.4% and 9.2% respectively). It yields plasma apolipoprotein A-I values that correlate highly with those obtained with polyclonal antibody (r = 0.96). So the use of well characterized monoclonal antibody mixtures reacting only to surface antigenic sites of apolipoprotein A-I present on native lipoprotein may provide the possibility of standardization of apolipoprotein A-I measurement.

Antibodies, Monoclonal↗