Biomedical subjects

J Dallongeville

Publications and source records attributed to J Dallongeville.

At least 73 records · Page 4Linked to original sources

PubMed1997

Effect of smoking cessation on lipoprotein A-I and lipoprotein A-I:A-II levels.

Cigarette smoking is associated with low plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein (apo) A-I levels, which may explain, in part, its deleterious effects on coronary heart disease (CHD). In a group of ex-smokers, we assessed the influence of smoking cessation on apo A-I particle levels. Plasma lipid, apolipoprotein, and lipoparticle concentrations of 58 subjects who had completely stopped smoking (ex-smokers) were compared with those of 37 subjects who had continued smoking (smokers) before and after a smoking cessation counseling program. Nutritional intake was recorded before and after the program to adjust for potential interaction with plasma lipid variables. Smokers and ex-smokers were similar in gender distribution, age, body mass index (BMI), social status, and nutrient intake. There were significantly greater increases in total cholesterol (P < .04), HDL-C (P < .005), HDL2-C (P < .008), and lipoprotein (Lp) A-I:A-II (P < .04) in ex-smokers than in smokers. After smoking cessation, ex-smokers consumed more vegetable protein (P < .02) and polysaccharides (P < .04) and had higher plasma levels of HDL-C (P < .0004), apo A-I (P < .001), Lp A-I (P < .007), and Lp A-I:A-II (P < .01) than smokers. Adjustments on nutritional variables did not show any additional difference between ex-smokers and smokers, suggesting that smoking per se effects Lp A-I and Lp A-I:A-II levels. In conclusion, HDL particles including Lp A-I and Lp A-I:A-II are higher in ex-smokers than in smokers.

Adult↗

PubMed1997

Adrenocorticotrophic hormone lowers serum Lp(a) and LDL cholesterol concentrations in hemodialysis patients.

Previously, we have shown that short-term administration of adrenocorticotrophic hormone (ACTH) results in reduced concentrations of apolipoprotein B-containing lipoproteins, including lipoprotein(a), and reduced activities of hepatic lipase. These effects were observed in steroid-treated patients suffering from iatrogenic ACTH deficiency and in healthy individuals. The direct nature of the influence of ACTH on hepatic lipoprotein metabolism was confirmed by in vitro experiments. The aim of the present investigation was to study the effects of ACTH treatment on uremic patients, who exhibit disturbed lipoprotein pattern due to the slow removal of triglyceride-rich lipoproteins and who probably are ACTH resistant. Eight patients on chronic hemodialysis were studied. After one intramuscular injection of Synacthen Depot (a synthetic ACTH1-24 preparation from Ciba Geigy AG, Basel, Switzerland) 1 mg, the only change noted was a significant reduction of 26% in median lipoprotein(a) concentration. After five injections, a further decrease (65%) was found in the lipoprotein(a) concentration. Also, reductions in median concentrations of total cholesterol, low density lipoprotein cholesterol and apolipoprotein B were observed. The magnitude of these changes was 15 to 30%. In contrast to previously studied groups, no changes were observed regarding triglyceride metabolism. Significantly increased median concentration of apolipoprotein CIII was found. However, the excess apolipoprotein CIII was confined to the fraction that was not associated with apolipoprotein B. Thus, administration of ACTH to uremic patients improved their atherogenic lipoprotein profile, a fact that may have future therapeutic implications. In comparison to previously studied groups, the uremic patients responded rather slowly and not at all regarding triglyceride metabolism.

Adrenocorticotropic Hormone↗

PubMed1997

Fat ingestion is associated with increased levels of apoC-III- and apoE-B-containing lipoprotein particles in humans.

Apolipoprotein (apo) C-III and apoE have a major influence on post-prandial apoB-containing lipoprotein metabolism. The goal of the present study was to compare the post-prandial changes in particles containing apoB and apoC-III and those containing apoB and apoE. Twenty subjects consumed a fatty meal (1 g of fat kg-1). Human lipoprotein particles were measured by enzyme-linked immunosorbent assay (ELISA) using combinations of anti-apoC-III, -apoE and -apoB. Post-prandial lipaemia was associated with an increase in LpC-III:B (+100%) and LpE:B (+55%; P < 0.05), which occurred 4.07 +/- 1.2 and 4.7 +/- 0.8 h after the meal respectively (P < 0.05). Gel filtration chromatography showed that fasting plasma LpC-III:B and LpE:B eluted in two fractions consisting of large and smaller sized particles; 3 h after the meal, LpC-III:B and LpE:B increased in the very low-density lipoprotein (VLDL) + intermediate-density lipoprotein (IDL) fraction; at 6 h, LpC-III:B and LpE:B decreased in VLDL and LpE:B increased moderately in the low-density lipoprotein (LDL) size range; at 10 h, both concentrations of lipoprotein particles returned to fasting levels. In conclusion, apoC-III-B-containing and apoE-B-containing lipoproteins have different post-prandial metabolic fates. These differences may result in different atherogenic potential.

Adult↗

PubMed1997

Postprandial lipaemia is associated with increased levels of apolipoprotein A-IV in the triacylglycerol-rich fraction and decreased levels in the denser plasma fractions.

Apolipoprotein (apo) A-IV is primarily associated with HDL or with the lipoprotein-free fraction of plasma, and in small amounts with chylomicrons and VLDL. The aim of the present study was to assess the effect of a fatty meal on the postprandial variation in plasma apo A-IV and on its distribution among lipoprotein fractions following absorption of fat. Twenty healthy male subjects participated in the study. After an overnight fast, subjects were given a fatty breakfast containing 1 g fat/kg body weight (% energy: fat 65, carbohydrate 20; protein 15). Blood samples were taken every hour during the next 10 h. Apo A-IV was measured by ELISA. Postprandial lipaemia was associated with a moderate, although significant, increase in the plasma levels of apo A-IV. Apo A-IV increased from the median baseline value of 0.15 g/l to 0.165 g/l (median +17%; P < 0.01) 5 h after fat ingestion. The postprandial peak of apo A-IV occurred 1 h after the triacylglycerol peak. There were no statistically significant correlations between baseline lipids, baseline apo A-IV and postprandial changes in apo A-IV levels, or between postprandial changes in lipids and apo A-IV at any time. To assess apo A-IV distribution among lipoproteins, plasma was fractionated by fast performance liquid chromatography at baseline and 3, 6 and 10 h postprandially. There was a substantial heterogeneity in the apo A-IV distribution among lipoproteins following the fatty meal. At 3 h after fat ingestion, apo A-IV levels increased in the triacyglycerol-rich lipoprotein (TRL) fraction and decreased in the denser plasma fraction. At 6 h after the fatty meal, apo A-IV was still present in the TRL but was decreased in the HDL fractions. The findings of the present study support the concept that apo A-IV particles transfer from the denser plasma fraction to TRL during postprandial lipaemia.

Adult↗

PubMed1997

Circadian variation of postprandial lipemia.

The goal of the present study was to assess the influence of mealtime on postprandial lipemia. Thirteen healthy subject aged 19-32 y were given the same meal at night (0100) or during the day (1300) in random order: the meal contained 40% of estimated daily energy expenditure. Blood samples were drawn at baseline and hourly for 8 h after the meal. Serum total cholesterol, very-low-density-lipoprotein cholesterol (VLDL-C), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triacylglycerols, VLDL-triacylglycerols, apolipoprotein (apo) A-I, and apo B were measured at each time point. In a subgroup of seven subjects a control fasting reference line was measured according to the same nocturnal and diurnal time schedule. The mean postprandial concentrations of triacylglycerol (P < 0.001), VLDL-triacylglycerol (P < 0.001), and VLDL-C (P < 0.001) were higher at night than during the day. In contrast, mean cholesterol (P < 0.01), LDL-C (P < 0.01), HDL-C (P < 0.001), apo A-I (P < 0.001), and apo B (P < 0.001) concentrations were lower after the night meal than after the day meal. The magnitude of the postprandial response was estimated by the area between the fasting and postprandial curves. The triacylglycerol and VLDL-triacylglycerol responses were not significantly different between night and day. The VLDL-C (P < 0.01) response was greater and LDL-C (P < 0.0001) and HDL-C (P < 0.01) responses were lower at night than during the day. These results indicate that circadian factors specifically affect serum cholesterol transport. Apo B (P < 0.01) and apo A-I (P < 0.01) responses followed LDL-C and HDL-C changes during the day but were dissociated from lipoprotein responses at night, suggesting that circadian apolipoprotein regulation is dissociated from that of serum lipids. The results of the present study indicate that postprandial lipid, lipoprotein, and apolipoprotein concentrations are affected by circadian factors.

Adult↗

PubMed1997

The role of a triplet repeat sequence of the very low density lipoprotein receptor gene in plasma lipid and lipoprotein level variability in humans.

The biological role of the very low density lipoprotein receptor (VLDL-R) in humans is not yet elucidated. This cellular receptor binds apolipoprotein E (apoE)-containing lipoparticles and is mainly expressed in peripheral tissues. The VLDL-R gene contains a polymorphic triplet (CGG) repeat located 19 bp upstream of the initiation codon. We explored the allelic distribution of this repeat in 1384 subjects of European Caucasian origin, 609 of them surviving a myocardial infarction. Six alleles corresponding to 5, 6, 7, 8, 9, and 11 repeats were detected in this population. The alleles 5, 8, and 9 were the most frequent, with frequencies of 0.413, 0.275, and 0.292, respectively. No association was found between the VLDL-R polymorphism and myocardial infarction. In controls without lipid lowering treatment, a statistically significant interaction between VLDL-R genotype and apoE phenotype was found for plasma triglycerides (P < .04), suggesting a gene-gene interaction. There was also a main effect of the VLDL-R polymorphism on LpE:B and LpA-I. The VLDL-R 9 allele was associated with lower levels of plasma LpE:B (P < .05) and higher concentrations of plasma LpA-I (P < .01) than the other alleles. These results suggest that VLDL-R has a modest influence on circulating lipoproteins in humans.

Adult↗

PubMed1996

Relevance of the quantification of apolipoprotein E in the cerebrospinal fluid in Alzheimer's disease.

Apolipoprotein E (Apo E), one of the major structural and functional apolipoproteins, has recently been implicated in the pathogenesis of Alzheimer's disease (AD). Several studies revealed that Apo E4 isoform is associated with the pathogenic process in AD. A significant reduction of cerebrospinal fluid (CSF) Apo E level in AD patients has been reported in two studies. To further investigate the physiopathological significance of such a variation of Apo E concentration in the CSF, we performed a quantification of Apo E by an enzyme linked immunosorbent assay (ELISA). There were no significant differences in CSF Apo E level between AD cases and control subjects or patients suffering from other neurological diseases. Gender, age and Apo E phenotype explained none of CSF Apo E concentration variability.

Aged↗

PubMed1996

Very-low-density lipoprotein of uremic patients is a poor substrate for bovine lipoprotein lipase in vitro.

Very-low-density lipoprotein (VLDL) from 10 hemodialysis patients and 10 healthy controls was studied with respect to the substrate characteristics for bovine milk lipoprotein lipase (LPL). Compared with the control subjects, the hemodialysis patients had significantly higher serum triglyceride and apolipoprotein B-associated apolipoprotein CIII concentrations (1.03 +/- 0.31 v 1.98 +/- 0.86 mmol/L and 0.004 +/- 0.002 v 0.011 +/- 0.005 g/L, respectively), lower serum high-density lipoprotein (HDL) cholesterol and apolipoprotein AI concentrations (1.33 +/- 0.37 v 0.95 +/- 0.31 mmol/L and 1.29 +/- 0.25 v 1.09 +/- 0.23 g/L, respectively), and lower postheparin plasma LPL activity (82 +/- 24 v 35 +/- 14 milliU/milliL). There were also significant increases in the relative fat content and diameter of VLDL particles from patients versus controls. VLDL was labeled with a fluorescent phospholipid analog, DHPE, and the rate of the lipolytic reaction with purified bovine milk LPL was estimated from the increase in fluorescence intensity at 490 nm. There was no significant difference between initial reaction velocities in the study groups, but VLDL particles from hemodialysis patients were lipolyzed to a significantly lesser extent than those from healthy controls (mean increase in fluorescence intensity after completion of the reaction, 95 +/- 36 v 140 +/- 43 arbitrary units). These results are in accordance with the accumulation of remnant particles reported to occur in uremia despite only a moderately increased serum triglyceride concentration.

Adolescent↗

PubMed1996

Retinoids increase human apolipoprotein A-11 expression through activation of the retinoid X receptor but not the retinoic acid receptor.

Considering the link between plasma high-density lipoprotein (HDL) cholesterol levels and a protective effect against coronary artery disease as well as the suggested beneficial effects of retinoids on the production of the major HDL apolipoprotein (apo), apo A-I, the goal of this study was to analyze the influence of retinoids on the expression of apo A-II, the other major HDL protein. Retinoic acid (RA) derivatives have a direct effect on hepatic apo A-II production, since all-trans (at) RA induces apo A-II mRNA levels and apo A-II secretion in primary cultures of human hepatocytes. In the HepG2 human hepatoblastoma cell line, both at-RA and 9-cis RA as well as the retinoid X receptor (RXR)-specific agonist LGD 1069, but not the RA receptor (RAR) agonist ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-pro penyl]-benzoic acid (TTNPB), induce apo A-II mRNA levels. Transient-transfection experiments with a reporter construct driven by the human apo A-II gene promoter indicated that 9-cis RA and at-RA, as well as the RXR agonists LGD 1069 and LG 100268, induced apo A-II gene expression at the transcriptional level. Only minimal effects of the RAR agonist TTNPB were observed on the apo A-II promoter reporter construct. Unilateral deletions and site-directed mutagenesis identified the J site of the apo A-II promoter mediating the responsiveness to RA. This element contains two imperfect half-sites spaced by 1 oligonucleotide. Cotransfection assays in combination with the use of RXR or RAR agonists showed that RXR but not RAR transactivates the apo A-II promoter through this element. By contrast, RAR inhibits the inductive effects of RXR on the apo A-II J site in a dose-dependent fashion. Gel retardation assays demonstrated that RXR homodimers bind, although with a lower affinity than RAR-RXR heterodimers, to the AH-RXR response element. In conclusion, retinoids induce hepatic apo A-II production at the transcriptional level via the interaction of RXR with an element in the J site containing two imperfect half-sites spaced by 1 oligonucleotide, thereby demonstrating an important role of RXR in controlling human lipoprotein metabolism. Since the J site also confers responsiveness of the apo A-II gene to fibrates and fatty acids via the activation of peroxisome proliferator-activated receptor-RXR heterodimers, this site can be considered a plurimetabolic response element.

Apolipoprotein A-II↗

PubMed1996

Alterations in plasma lipoproteins and apolipoproteins before the age of 40 in heterozygotes for lipoprotein lipase deficiency.

We have assessed the expression of heterozygosity for lipoprotein lipase (LPL) deficiency by studying a single large French Canadian family comprising 92 persons including 21 carriers of the catalytically defective P207L mutation. Phenotypic changes distinguishing heterozygotes from controls were seen early, before the age of 40 and often before 20 years of age. In the total cohort these changes included an elevation in the mean very low density (VLDL) and intermediate density lipoprotein (IDL) triglyceride (+69%; P = 0.01 and +40%; P = 0.001) and cholesterol (+51%; P = 0.03 and +67%; P = 0.007) and apoB levels but decreased HDL2 and HDL3 cholesterol, (-32%; P = 0.01 and -15%; P = 0.002 respectively). While the lipid compositions of VLDL and IDL were similar between heterozygotes and controls, the low density (LDL) and high density lipoproteins (HDL) of carriers were triglyceride enriched. Heterozygotes also had a markedly lower apoC-III ratio (apoC-III in supernatant/apoC-III in heparin precipitate) (1.46 vs. 3.86 P = 1 x 10(-4)) indicating a substantial enrichment of VLDL and IDL with apoC-III and depletion of HDL apoC-III supporting this ratio as an effective index for efficiency of lipolysis. LpA-I was markedly reduced (0.34 vs. 0.43 P = 1 x 10(-5)) showing that levels of this particle are partly dependent on LPL catalytic activity. Heterozygotes manifest from an early age with a markedly reduced HDL, LpA-I, apoC-III ratio and an increased TC/HDLc ratio which would predict a relatively increased risk of premature coronary artery disease, compared to their normal siblings.

Adult↗

PubMed1996

Lipoprotein(a) as a marker for coronary heart disease.

Lipoprotein(a) (Lp(a)) resembles a low-density lipoprotein (LDL) particle, but with the addition of apolipoprotein(a). Apolipoprotein(a) (apo(a)) is homologous to plasminogen, and its similarity to plasminogen indicates a prothrombogenic role for Lp(a), whereas the similarity of Lp(a) to LDL suggests a proatherogenic role. Thus, Lp(a) is a link between atherosclerosis and thrombosis. The apo(a) gene is highly polymorphic, and a relationship exists between the different apo(a) alleles and plasma Lp(a) levels. There is also evidence to suggest an association between serum Lp(a) concentration and the frequency of cardiovascular atherosclerosis, particularly myocardial infarction in men, although some of the recently published epidemiological studies have been controversial. The heightened awareness of increased Lp(a) levels being a risk factor for coronary artery disease has led to the evaluation of the effects of lipid-lowering agents on Lp(a) levels. The data that have emerged, however, are conflicting, and are derived mostly from short-term studies involving the use of statins. Our group has studied the short- and long-term effect of fluvastatin on Lp(a) in hypercholesterolaemic patients; fluvastatin was found to have no effect in such patients as observed in the short-term studies, but significant reductions in Lp(a) levels were noted during long-term treatment. Although our findings are in agreement with those of a previously published report, there is still a great need to confirm the data that have been reported in separate studies.

Biomarkers↗

PubMed1996

Cigarette smoking is associated with differences in nutritional habits and related to lipoprotein alterations independently of food and alcohol intake.

OBJECTIVE: To assess the effects of smoking on serum lipoprotein levels taking into account current nutritional intakes. DESIGN: Case-control study comparing smokers and non-smokers. SETTING: Ambulatory subjects of the Urban Community of Lille examined at home or at the Health Care Center. SUBJECTS: Men, between 45 and 65 years of age; n = 89 smokers (cases) and n = 91 non-smokers (controls); non-smokers were randomly selected from the voter's registration lists, 7 smokers and 2 non-smokers were excluded for hyperlipidemia. INTERVENTIONS: Blood sampling, medical examination and three-day food records validated by a registered dietician. RESULTS: Smokers were younger (P < 0.001) and thinner (P = 0.003), chose more frequently visible fats of animal origin (P = 0.03) and reported significantly larger daily meat servings (P = 0.01) than non-smokers. Smokers had a significantly higher intake of non-alcoholic energy (P < 0.05), lipids of animal origin (P = 0.003), saturated fat (P < 0.01) and monounsaturated fat (P < 0.01) and a lower P/S ratio (P = 0.02) than non-smokers. After adjustment on age and body mass index, smokers had significantly higher levels of mean serum triglycerides (P = 0.03), VLDL-cholesterol (P = 0.0003) and systolic blood pressure (P = 0.02) and lower values of HDL-cholesterol (P = 0.02) than non-smokers. Additional adjustment for alcohol consumption showed significantly lower apo A-I values (P = 0.03) in smokers than non-smokers. Further adjustment for the intake of lipids of animal origin revealed higher apo B values (P = 0.04) in smokers than non-smokers. CONCLUSIONS: (1) Smoking is associated with serum lipid and lipoprotein alterations independently of nutritional factors, (2) Nutritional habits of smokers are less 'healthy' than those of non-smokers (3) Smokers is a group of particular importance in terms of multifactorial public health intervention.

Aged↗

PubMed1995

Changes in plasma apolipoprotein B-containing lipoparticle levels following therapy with fluvastatin and cholestyramine. European Fluvastatin Study Group.

Epidemiologic studies have demonstrated that apolipoprotein (apo) B-containing lipoparticles (LpE:B, LpC-III:B) are associated with the risk of coronary artery disease whereas apo A-1-containing lipoparticles (LpA-I) are protective against coronary artery disease. The effect on lipoparticle levels of the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor fluvastatin, in combination with cholestyramine, was assessed in a double-blind randomized study. A total of 144 patients with primary hypercholesterolemia were recruited, who had successfully completed an original study comparing the effects of fluvastatin and cholestyramine on plasma lipoparticle levels. All subjects fulfilled the following inclusion criteria: plasma low density lipoprotein cholesterol (LDL-C) levels > 160 mg/dL, with premature coronary artery disease and 2 associated risk factors; or LDL-C > 190 mg/dL, no coronary artery disease, and triglycerides < 300 mg/dL, after a lipid-lowering diet. Patients were randomized to 1 of 3 combination therapy groups: fluvastatin 20 mg/day plus cholestyramine 4 g/day; fluvastatin 20 mg/day plus cholestyramine 8 g/day; and fluvastatin 20 mg/day plus cholestyramine 16 g/day. The study length was 6 weeks and patients were examined at 3-week intervals. Fluvastatin plus cholestyramine produced a significant (p < 0.001), dose-dependent reduction in levels of cholesterol (range, -29 to -34%), LDL-C (range, -30 to -44%), apo B (range, -23 to -34%), and apo E (range, -33 to -43%). LpE:B levels were also reduced (range, -19 to -26%), but not significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticholesteremic Agents↗

PubMed1995

Multiple coronary heart disease risk factors are associated with menopause and influenced by substitutive hormonal therapy in a cohort of French women.

The relationship between menopause and cardiovascular risk factors of progestin alone or in combination with estrogen were analysed in a sample of French women. Three thousand four hundred and forty consecutive women, between 45 and 65 years of age, who received a systematic check-up between January 1991 and April 1993 were enrolled in this study. All biological measurements were performed at a central laboratory. Women were classified as premenopausal (n = 1233), postmenopausal (n = 1774) if they had not menstruated in the 12 months before examination, and perimenopausal (n = 433) if they met at least two of the following criteria: elevated levels of serum follicle-stimulating hormone (FSH), irregular menses, amenorrhea for less than 12 months, hot flushes. The effect of menopause on cardiovascular risk factors was determined in 2167 women between 45 and 65 years of age (premenopausal n = 790, postmenopausal n = 1377), none of whom were presently treated with hormonal replacement therapy (HRT). In addition, the effect of progestin was assessed in a group or 397 perimenopausal women, and the effect of combined estrogen and progestin replacement therapy in another group of 1746 postmenopausal women. Menopause was associated with higher levels of serum cholesterol (6.4 vs. 5.9 mmol/l), triglycerides (1.2 vs. 1.0 mmol/l), apolipoprotein (apo) B (1.3 vs. 1.1 g/l), apo A-I (1.9 vs. 1.8 g/l), as well as with elevated diastolic blood pressure (79.7 vs. 77.0 mmHg). Multivariate analysis indicated that these effects were independent of age, body mass index (BMI), glycemia, smoking, alcohol intake, exercise and parity. Perimenopausal women treated with progestin alone (n = 95) were compared to perimenopausal women not using HRT (n = 302). There were no statistically significant differences in the levels of cholesterol, triglycerides, apo B, apo A-I, glycemia and blood pressure between the two groups. Postmenopausal women using a combination of estrogen and progestin (n = 369) had significantly lower levels of serum cholesterol (6.1 vs 6.4 mmol/l), triglycerides (1.0 vs. 1.2 mmol/l), apo B (1.2 vs. 1.3 g/l), systolic (131.9 vs. 137.9 mmHg) and diastolic (76.9 vs. 79.7 mmHg) blood pressure than postmenopausal women without hormonal therapy (n = 1377), taking into account confounding variables. In contrast, serum apo A-I levels were not altered by the combined hormonal therapy. We conclude that menopause is associated with the aggravation of multiple cardiovascular risk factors. These deleterious factors are affected by a treatment of combining estrogen and progestin.

Aged↗

PubMed1995

Comparison of the effect of fluvastatin, an hydroxymethyl glutaryl coenzyme A reductase inhibitor, and cholestyramine, a bile acid sequestrant, on lipoprotein particles defined by apolipoprotein composition.

In a double-blind, parallel-group, randomized study, the effects of fluvastatin (FLUV) 20 and 40 mg/d on lipoprotein particle levels were compared with those of cholestyramine (CME) 16 g/d. Lipoparticles were defined by apolipoprotein composition as either those containing both apolipoprotein (apo) B and apo E or CIII (lipoprotein [Lp] E-B or Lp CIII-B) or those containing apo AI alone (Lp AI) or in association with apo AII (Lp AI-AII). After an 8-week dietary stabilization period, 100 hypercholesterolemic patients were treated with FLUV 20 mg/d for 6 weeks and 40 mg/d for an additional 6 weeks and were compared with 48 hypercholesterolemic subjects treated with CME 16 g/d. Treatment with FLUV (40 mg/d) or CME (16 g/d) for 12 weeks was associated with a significant reduction in plasma cholesterol and low-density lipoprotein (LDL) cholesterol and a significant increase in high-density lipoprotein (HDL) cholesterol. However, plasma triglyceride levels decreased following FLUV treatment, whereas they increased with CME. These changes were associated with a significant reduction in the levels of apo B (FLUV, -24%, P < .001; CME, -26%, P < .001), apo E (FLUV, -36%, P < .001; CME, -32%, P < .001), and apo CIII (FLUV, -21%, P < .001; CME, -6%, NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Evidence that reduced lipoprotein lipase activity is not a primary pathogenetic factor for hypertriglyceridemia in renal failure.

The aim of the study was to document postheparin plasma lipoprotein lipase (LPL) and hepatic lipase activities and relate these to serum lipid, lipoprotein and apolipoprotein concentrations in 85 patients with kidney function ranging from normal to dialysis dependency. Strict selection criteria were applied in order to exclude conditions other than renal failure which may influence lipid metabolism. Stress was laid on minimizing proteinuria and inflammatory activity. The changes in the lipoprotein pattern were numerically strikingly modest compared to those previously reported. This probably reflected the intention to elucidate the contribution of reduced renal function as such to the dyslipoproteinemia of renal failure, a condition often associated with confounding factors. Significant increases in serum concentrations of triglycerides and apolipoprotein CIII were already observed in moderate renal failure, whereas serum concentrations of high density lipoprotein cholesterol and plasma LPL activities were decreased only in severe renal failure. Plasma LPL activities were not significantly reduced in hemodialysis patients (probably due to anticoagulation with low molecular weight heparin), but serum concentrations of triglycerides and apolipoprotein CIII were significantly increased. A multiple regression analysis, taking glomerular filtration rate, LPL and apolipoprotein CIII into account, showed that both plasma LPL activity and serum apolipoprotein CIII concentration independently predicted serum triglyceride concentration. However, serum apolipoprotein CIII concentration was a much stronger predictor than plasma LPL activity. Thus, a decrease in LPL activity does not seem to be a prerequisite for the hypertriglyceridemia of uremia, but it probably accentuates this condition.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1995

Apolipoprotein A-I-containing lipoproteins and atherosclerosis.

Apolipoprotein A-I-containing lipoproteins represent a heterogeneous group of lipoparticles. Recent studies suggest that a specific subpopulation within the lipoprotein (AI) subclass may be more effective than other lipoproteins in promoting cholesterol efflux from cells and in the different steps of reverse cholesterol transport. This review describes the different apolipoprotein A-I-containing HDL subfractions, their role in reverse cholesterol transport, and their metabolic interconversions and relationship with lipoprotein-modifying enzymes.

Animals↗

PubMed1995

Fibrates downregulate apolipoprotein C-III expression independent of induction of peroxisomal acyl coenzyme A oxidase. A potential mechanism for the hypolipidemic action of fibrates.

Epidemiological and transgenic animal studies have implicated apo C-III as a major determinant of plasma triglyceride metabolism. Since fibrates are very efficient in lowering triglycerides, it was investigated whether fibrates regulate apo C-III gene expression. Different fibrates lowered rat liver apo C-III mRNA levels up to 90% in a dose- and time-dependent manner, whereas intestinal apo C-III mRNA remained constant. This decrease in liver apo C-III mRNA was rapid (1 d) and reversible, since it was restored to control levels within 1 wk after cessation of treatment. In addition, fenofibrate treatment abolished the developmental rise of hepatic apo C-III mRNA observed during the suckling-weaning period. Administration of fibrates to rats induced liver and intestinal expression of the acyl CoA oxidase gene, the rate-limiting enzyme for peroxisomal beta-oxidation of fatty acids. In primary cultures of rat and human hepatocytes, fenofibric acid lowered apo C-III mRNA in a time- and dose-dependent manner. This reduction in apo C-III mRNA levels was accompanied by a decreased secretion of apo C-III in the culture medium of human hepatocytes. In rat hepatocytes fenofibric acid induced acyl CoA oxidase gene expression, whereas acyl CoA oxidase mRNA remained unchanged in human hepatocytes. Nuclear run-on and transient transfection experiments of a reporter construct driven by the human apo C-III gene promoter indicated that fibrates downregulate apo C-III gene expression at the transcriptional level. In conclusion, these studies demonstrate that fibrates decrease rat and human liver apo C-III gene expression. In humans the mechanisms appears to be independent of the induction of peroxisomal enzymes. This downregulation of liver apo C-III gene expression by fibrates may contribute to the hypotriglyceridemic action of these drugs.

Acyl-CoA Oxidase↗