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J Dallongeville

Publications and source records attributed to J Dallongeville.

87 records · Page 5Linked to original sources
PubMed1995

Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.

In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia, the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein (apo) A-II, a major protein constituent of HDL. Administration of fenofibrate (300 mg/d) to 16 patients with coronary artery disease resulted in a marked increase in plasma apo A-II concentrations (0.34 +/- 0.11 to 0.45 +/- 0.17 grams/liter; P < 0.01). This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II production, since fenofibric acid induced apo A-II mRNA levels to 450 and 250% of control levels in primary cultures of human hepatocytes and in human hepatoblastoma HepG2 cells respectively. The induction in apo A-II mRNA levels was followed by an increase in apo A-II secretion in both cell culture systems. Transient transfection experiments of a reporter construct driven by the human apo A-II gene promoter indicated that fenofibrate induced apo A-II gene expression at the transcriptional level. Furthermore, several other peroxisome proliferators, such as the fibrate, Wy-14643, and the fatty acid, eicosatetraynoic acid (ETYA), also induced apo A-II gene transcription. Unilateral deletions and site-directed mutagenesis identified a sequence element located in the J-site of the apo A-II promoter mediating the responsiveness to fibrates and fatty acids. This element contains two imperfect half sites spaced by 1 oligonucleotide similar to a peroxisome proliferator responsive element (PPRE). Cotransfection assays showed that the peroxisome proliferator activated receptor (PPAR) transactivates the apo A-II promoter through this AII-PPRE. Gel retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE. In conclusion, in humans fibrates increase plasma apo A-II concentrations by inducing hepatic apo A-II production. Apo A-II expression is regulated at the transcriptional level by fibrates and fatty acids via the interaction of PPAR with the AII-PPRE, thereby demonstrating the pivotal role of PPAR in controlling human lipoprotein metabolism.

5,8,11,14-Eicosatetraynoic Acid↗
PubMed1994

Fluvastatin reduces levels of plasma apo B-containing particles and increases those of LpA-I. European Fluvastatin Study Group.

Epidemiologic studies have demonstrated an association between apolipoprotein (apo) B-containing particles (lipoprotein [Lp] E:B; LpC-III:B) and an inverse association between LpA-I and the risk of coronary artery disease (CAD). The effect of 6 weeks of treatment with fluvastatin (20 and 40 mg/day in the evening), a novel competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, on lipoparticle levels was studied in 423 patients with hypercholesterolemia after 14 weeks of standard dietary therapy. The combined data of the European double-blind controlled studies were used for the analysis. Two independent groups of hypercholesterolemic patients receiving fluvastatin (20 and 40 mg every evening) for 6 weeks were compared with a placebo group. For inclusion, patients had to fulfill the following criteria: plasma low-density lipoprotein (LDL) cholesterol levels > 160 mg/dL and premature CAD and/or two associated risk factors; LDL cholesterol > 190 mg/dL and no CAD; triglycerides < 300 mg/dL. All measurements were performed at the Pasteur Institute Central Laboratory, LpE:B and LpC-III:B were measured by double-site ELISA. Lipoprotein A-I and LpA-I:A-II were determined by differential electroimmunodiffusion. Treatment with 20 and 40 mg of fluvastatin was associated with reductions in plasma apo B (median change: -19.3% and -22.8%, respectively; p < 0.001), LpE:B (-12.5% and -22.6%, respectively; p < 0.001), and LpC-III:B (-3.6% and -36.8%, respectively; p < 0.001) particles compared with placebo. Significant increases in plasma apo A-I (1.7% and 4.8%, respectively; p < 0.001) and antiatherogenic LpA-I (2.3% and 6.9%, respectively; p < 0.001) were also observed. Levels of LpA-I:A-II were not affected by fluvastatin treatment. In conclusion, 6-week treatment with fluvastatin is associated with beneficial antiatherogenic changes in lipoparticle profiles in hypercholesterolemic patients.

Analysis of Variance↗
PubMed1994

Short-term response to dietary counseling of hyperlipidemic outpatients of a lipid clinic.

OBJECTIVE: To evaluate the efficacy of a limited dietary intervention delivered by dietitians in a single counseling session on plasma lipid levels in free-living subjects with hyperlipidemia. DESIGN: A 2-month, nonrandomized comparative study of dietary counseling efficacy in subjects with hyperlipidemia. Dietary instruction was conducted in a lipid clinic by dietitians. Subjects were instructed to follow a diet low in saturated fat and cholesterol (National Education Cholesterol Program step 1 or 2 diets) for 2 months with concomitant energy restriction for weight reduction when necessary. Another group of patients who did not receive dietary counseling during the same period served as a control. SUBJECTS: Ambulatory patients were recruited from the Lipid Clinic of the Montreal Clinical Research Institute. INTERVENTION: Dietary counseling was provided to 104 subjects with hypercholesterolemia and 113 subjects with hypertriglyceridemia. They were compared with 72 subjects with hypercholesterolemia and 80 subjects with hypertriglyceridemia who did not receive dietary counseling. RESULTS: In the hypercholesterolemic group, significant reductions in plasma cholesterol (mean +/- standard deviation = -5.7 +/- 11.7%) and low-density lipoprotein cholesterol (LDL-C) (-7.3 +/- 14.2%) and no changes in plasma very-low-density lipoprotein cholesterol (VLDL-C) or high-density lipoprotein cholesterol (HDL-C) were observed after dietary counseling. The LDL-C response to diet was normally distributed, and 20% of the individuals with hypercholesterolemia reached LDL-C levels below 4.1 mmol/L. In patients with hypercholesterolemia and no clinical evidence of familial hypercholesterolemia, (n = 76) the reductions in plasma cholesterol (-6.6 +/- 10.8%) and LDL-C (-8.2 +/- 14%) were more pronounced. Among the latter patients, 27.6% reached LDL-C levels below 4.1 mmol/L. In subjects with hypertriglyceridemia, the reductions in plasma cholesterol (-4.8 +/- 12.8%), triglycerides (-20.7 +/- 33%), and VLDL-C (-19.5 +/- 29%) were associated with an increase in LDL-C (+8.5 +/- 25.7%) and HDL-C (+5.5 +/- 18%). Of the subjects with hypertriglyceridemia, 20% had triglyceride levels below 2.3 mmol/L after treatment. No significant changes were observed in the control groups during the same period. CONCLUSIONS: Dietary counseling of subjects with hypercholesterolemia or hypertriglyceridemia was associated with beneficial changes in plasma lipid levels after 2 months of dietary intervention. However, longer and more controlled dietary interventions are necessary for most patients to achieve lipid goals.

Adult↗
PubMed1994

Effect of fluvastatin on plasma apolipoprotein-B-containing particles, including lipoprotein(a). European Fluvastatin Study Group.

Epidemiological studies have demonstrated an association between apolipoprotein-(apo)-B containing particles [lipoprotein (Lp) (a), LpE:B; LpC-III:B] and coronary heart disease (CHD). The effect of fluvastatin, a novel competitive inhibitor of HMG-CoA reductase, on these plasma lipoprotein levels was studied in patients with hypercholesterolaemia after 14 weeks of standard dietary therapy. The results of a placebo-controlled, dose-response study and of the combined data of the European double-blind, controlled studies on the effect of fluvastatin are presented. The patients were selected according to the following criteria of inclusion: plasma low-density-lipoprotein (LDL) cholesterol levels > 160 mg dL-1 and premature CHD and/or two associated risk factors, or LDL cholesterol > 190 mg dL-1 and no CHD, plus triglycerides < 300 mg dL-1. All measurements were performed at the Pasteur Institute Central Laboratory. Lp(a), LpE:B and LpC-III:B particles were measured by double-site ELISA. In the placebo-controlled, dose-response study, 429 subjects were randomly assigned to one of the following treatment groups: placebo, fluvastatin 2.5 mg q.p.m., 5 mg q.p.m., 10 mg q.p.m. and 20 mg q.p.m. Treatment with fluvastatin for 6 weeks was associated with a dose-dependent reduction of LDL cholesterol, apoB, LpE:B and LpCIII:B levels. In addition, treatment with fluvastatin 5 mg and 20 mg q.p.m. was associated with a significant reduction in median Lp(a) concentrations (3.2%, P < 0.05 and 6.4%, P < 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Apolipoprotein(a) is present in the triglyceride-rich fraction in type IV hypertriglyceridemia.

This study was designed to quantify the levels of apo(a) and assess their distribution among lipoprotein fractions in type IV hypertriglyceridemia. Plasma density < 1.006 g/mL fraction (VLDL) was obtained by preparative and zonal ultracentrifugation. Apo(a) was detected by immunoblotting with anti-apo(a) antibodies of agarose gel electrophoresed lipoproteins. Apo(a) was consistently found in VLDL in 30 hypertriglyceridemic subjects, but not in 10 normolipidemic or 10 hypercholesterolemic subjects with normal triglyceride levels. Apo(a)B particle concentrations were then measured using a selective 'sandwich' ELISA with anti-apo(a) as the capture antibody and anti-apoB as the detecting antibody. The mean apo(a)B level of VLDL in six hypertriglyceridemic patients was 30% (range 1.3-50%) of the total plasma concentration. Apo(a)-containing particles of both plasma, d < 1.006 g/mL and d > 1.006 g/mL, had the same pre-beta mobility on agarose gel electrophoresis and a similar apparent molecular weight on non-denaturing 2-16% gradient polyacrylamide gel electrophoresis. Fractionation of plasma by zonal ultracentrifugation confirmed the presence of a heterogeneous distribution of apo(a) in hypertriglyceridemic subjects. Apo(a) was present throughout the density range from VLDL to Lp(a). After normalization of plasma triglyceride levels with dietary fish oil, apo(a) was no longer detected in VLDL suggesting that detection of apo(a) in the plasma, d < 1.006 g/mL, density fraction is related to type IV hypertriglyceridemia.

Cholesterol↗
PubMed1992

ACAT activity in freshly isolated human mononuclear cell homogenates from hyperlipidemic subjects.

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes the esterification of cholesterol in human mononuclear cells (MNC). In order to assess the relationship between lipid levels and ACAT activity in circulating MNC, we measured the rate of [14C]oleoyl-CoA incorporation into cholesterol ester in freshly isolated MNC homogenates from hyperlipidemic subjects. Baseline, off-treatment results obtained in 14 hypertriglyceridemic subjects (eight type IV and six type III) and seven subjects with familial hypercholesterolemia (FH) due to the same deletion of greater than 10 kb on the low-density lipoprotein (LDL)-receptor gene were compared with values determined in 12 healthy normolipidemic subjects. The rate of cholesterol esterification was 45 +/- 28 pmol/5 min/mg cell protein in healthy normolipidemic controls. This rate was significantly higher in type IV subjects (84 +/- 52 pmol/5 min/mg cell protein, P less than .05) and FH subjects (67 +/- 25 pmol/5 min/mg cell protein, P less than .05). The values were more dispersed in type III subjects; the mean value for the group (72 +/- 46 pmol/5 min/mg cell protein) was not statistically different from the control. Hypertriglyceridemic patients were then treated with 6 g/d of omega-3 fatty acids. This resulted in a significant reduction in plasma total triglycerides and very-low-density lipoprotein (VLDL)-cholesterol in both type III subjects (-57% and -51%, P less than .05) and type IV subjects (-62% and -62%, P less than .01). The reduction in VLDL concentration was associated with a significantly lower ACAT activity in MNC homogenates from type IV subjects (from 84 +/- 52 to 60 +/- 36 pmol/5 min/mg cell protein, P less than .05), but not from type III hypertriglyceridemic subjects (from 72 +/- 46 to 73 +/- 36 pmol/5 min/mg cell protein). In conclusion, we found that cholesterol esterification in human MNC is elevated in hyperlipidemic subjects and can be decreased with normalization of lipid levels. However, ACAT activity changes occurring with treatment are heterogeneous among hyperlipidemic subjects, suggesting that factors other than plasma lipid level reduction affect ACAT activity in vivo.

Cholesterol↗
PubMed1992

Modulation of plasma triglyceride levels by apoE phenotype: a meta-analysis.

The relationship between apoE phenotype and plasma lipid levels was analyzed in the combined data of published studies. Accordingly, 45 population samples from 17 different countries were included in the analysis. The mean plasma values of cholesterol (CH), triglyceride (TG), and high density lipoprotein (HDL)-CH of the apoE 2/2, 3/2, 4/3, 4/4, and 4/2 groups were compared with the same parameters of the E 3/3 subset. The standardized difference between the plasma lipid concentrations of the apoE subgroups and of their respective apoE 3/3 control (Z-score), as well as their mean weighted value, were calculated for each study and in each subgroup. The analysis confirmed that subjects carrying the epsilon 2 and epsilon 4 alleles had, respectively, lower (Z2/2 = -0.39, Z3/2 = -0.34) and higher (Z4/3 = 0.15, Z4/4 = 0.29) plasma cholesterol values than subjects carrying the epsilon 3/epsilon 3 genotype. In addition, results indicated a consistent relationship between plasma TG levels and apoE phenotype among different populations. TG concentrations were significantly higher in apoE 2/2, 3/2, 4/3 and E 4/2 than in E 3/3 subsets (Z2/2 = 0.42, Z3/2 = 0.14, Z4/3 = 0.13, Z4/2 = 0.19). Further, this trend was found in samples of normolipidemic adults and children, in diabetic and obese individuals, as well as in hyperlipidemic subjects indicating an ubiquitous relationship. Concurrently, HDL-CH was significantly lower in the apoE 4/3 (Z4/3 = -0.09) than in the E 3/3 subset.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

The relation between triglyceride synthesis in peripheral tissues and postprandial plasma triglyceride levels: preliminary evidence of a role for acylation stimulating protein.

The present study examines the hypothesis that the rate at which peripheral tissues synthesize triglycerides is a key determinant of the rate at which they are removed from plasma. The cells of greatest interest in this regard would, of course, be the adipocytes. However, serial sampling of this tissue is not possible in man. We have approached the question indirectly, by studying triglyceride synthesis in human mononuclear cells before and after an oral fat load. In addition, plasma levels of Acylation Stimulating Protein (ASP) were measured after an overnight fast and 4 h after ingestion of the oral fat load. Similar measurements were made in the same subjects after fasting overnight and with the fast extended for 4 additional hours. With the extended fast, no parameter measured changed significantly. However, after the oral fat load, the following changes were found to be significant: plasma triglycerides increased (63.6 +/- 31.1 vs 101.5 +/- 43 mg/dl, p less than 0.005) as did d less than 1.006 g/ml triglycerides (42.3 +/- 22.8 vs 78.0 +/- 39.7 mg/dl, p less than 0.005) and plasma ASP (10.4 +/- 2.2 vs 14.7 +/- 2.3 mg/dl, p less than 0.005). In addition, the rate of triglyceride synthesis in the mononuclear cells increased significantly (1.22 +/- 0.3 vs 1.52 +/- 0.3 nmol oleate/mg cell protein per h, p less than 0.005). There was also a significant inverse relation between the increase in the d less than 1.006 triglycerides between 0 and 4 h and the increase in triglyceride synthesis in the mononuclear cells (r = 0.91, p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Acylation↗
PubMed1991

A phenocopy of type III dysbetalipoproteinemia occurring in a candidate family for a putative apo E receptor defect.

On theoretical grounds, an apo E receptor defect should be manifested by the accumulation of lipoprotein remnants that are normally cleared by this receptor and cannot be processed by the normal apo B, E receptor (LDL-receptor). Furthermore, the defect should not be selective for a specific apo E phenotype since none of the isoforms would be cleared preferentially. Our search for such an occurrence led us to the discovery, in five members of a family of ten, of a unique dyslipoproteinemia mimicking type III. As in type III, plasma levels of cholesterol, triglycerides, VLDL-cholesterol, VLDL-triglycerides and apo E, as well as the VLDL-C/TG ratio, were high. LDL-cholesterol and HDL-cholesterol tended to be low. The clearance of plasma triglycerides after a fat load was impaired. Tubero-eruptive xanthomas, arcus corneae and manifestations of atherosclerosis were present in some individuals. In contrast to type III, the dyslipoproteinemia occurred in subjects bearing three different apo E phenotypes: E4/2, E4/3 and E3/2. VLDL-apo B levels were markedly increased, the VLDL-C/VLDL-B ratio was low and a double pre-beta band was present on lipoprotein electrophoresis. In spite of high apo E and borderline high apo CIII plasma levels, levels of the lipoprotein particles LpCIII:B and LpE:B, which characterize type III, were not raised. Rapid weight loss or treatment with a fibrate was observed to normalize the lipoprotein profile. It is surmised that the apo E-rich lipoprotein particles accumulating in this type III phenocopy with "hyperapoprebetalipoproteinemia" could be those that are normally cleared by an apo E receptor.

Adult↗
PubMed1990

Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells.

We studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [14C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol (r = 0.65 p less than 0.0003). These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans.

Cholesterol↗
PubMed1989

Iron deficiency among active men.

Iron deficiency in active men is well documented. To assess the relative importance of dietary iron intake, iron absorption, and iron loss in the pathogenesis of this iron deficiency, we compared a group of iron-deficient athletes to a group with normal iron stores. Iron absorption was assessed by an iron tolerance test. Serum haptoglobin was used as a measure of hemolysis. The presence of hemoglobinuria reflected urinary iron loss. Iron intake was determined by a 3-day dietary record as well as a food frequency questionnaire. Results showed iron absorption to be inversely correlated with iron stores. Iron-deficient athletes had higher absorption, suggesting a normal regulation mechanism. Major hemolysis (serum haptoglobin below 40 mg/dl) was found in 28% of subjects with no relationship to iron stores. No hemoglobinuria was detected after a usual training session. Iron intake was elevated in relation to high caloric intake, but iron intake in the form of meat was lower in iron-deficient athletes, as compared to those with normal or repleted iron stores. It is our opinion that inadequate iron intake is an important determinant of iron deficiency in athletes.

Absorption↗
PubMedDate not supplied

Apolipoprotein E polymorphism association with lipoprotein profile in endogenous hypertriglyceridemia and familial hypercholesterolemia.

Apolipoprotein (apo) E polymorphism was among the first-reported genetic polymorphisms that explained part of the normal variation in plasma cholesterol concentrations in humans. The aim of this study was to assess the influence of allelic variation at the apo E gene locus on the plasma lipoprotein profile in hyperlipidemia. The lipoprotein levels of hyperlipidemic subjects of the major apo E phenotypes (E3/2, E3/3, and E4/3) were compared. One hundred eighty-two subjects with endogenous hypertriglyceridemia and 98 subjects with familial hypercholesterolemia due to a 10-kb deletion in their low density lipoprotein (LDL) receptor genes were compared with 424 normolipidemic controls from the same environmental background. LDL concentrations were lower in the E3/2 subset than in the E3/3 or E4/3 subset in the control, hypertriglyceridemic, and familial hypercholesterolemic groups. In absolute values, the magnitude of the effect was greatest in the familial hypercholesterolemic group. However, the direction and percentage change were identical in the presence or absence of the LDL receptor defect, indicating that the apo E phenotype effect is independent of LDL receptor status. Triglyceride and very low density lipoprotein (VLDL) cholesterol concentrations were higher in E3/2 than in E3/3 or E4/3 hypertriglyceridemic subjects, but this difference was not found in the familial hypercholesterolemic or control group. Thus, there seems to be a specific interaction between apo E isoforms and VLDL metabolism in hypertriglyceridemia; allelic variation at the apo E gene locus seems to be associated with specific alterations in the plasma lipoprotein profile of subjects with well-defined types of hyperlipidemia.

Adult↗
PubMedDate not supplied

Fish oil supplementation reduces beta-very low density lipoprotein in type III dysbetalipoproteinemia.

beta-Very low density lipoproteins (beta-VLDLs) are atherogenic, cholesterol-rich chylomicron and VLDL remnants that accumulate in the plasma of type III dysbetalipoproteinemic subjects. To evaluate the effect of fish oil supplementation on plasma beta-VLDL concentrations, we compared the lipid and lipoprotein responses in nine type III and nine type IV hyperlipidemic subjects. Each individual received 6 g/day omega-3 fatty acids for 12 weeks. Before treatment, the mean total cholesterol, total triglyceride, VLDL triglyceride, low density lipoprotein (LDL) cholesterol, and high density lipoprotein (HDL) cholesterol levels were not different between groups. Conversely, VLDL cholesterol, intermediate density lipoprotein (IDL) cholesterol, and IDL triglycerides were higher in type III than in type IV subjects. Fish oil supplementation was associated with significantly lower levels of cholesterol (-50%), triglycerides (-50%), and apolipoprotein B (-50%) in the d less than 1.006 g/ml ultracentrifugation plasma fraction in both groups, compatible with a reduction in VLDL in type III and type IV subjects, and in beta-VLDL in type III subjects. This finding was confirmed by analysis of the plasma zonal ultracentrifugation profile and the agarose gel electrophoretic pattern of lipoproteins, which showed a reduction in but not a disappearance of remnant particles, suggesting that not all beta-VLDL had been cleared after treatment. The levels of IDL cholesterol and IDL triglycerides (1.006 less than d less than 1.019 g/ml) were not affected in either group. Initially low LDL cholesterol (1.019 less than d less than 1.063 g/ml) and HDL cholesterol levels rose significantly in both groups. In type III hyperlipidemics, all LDL cholesterol values remained below 120 mg/dl, whereas they were higher than 150 mg/dl after treatment in two individuals with type IV hyperlipidemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗