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Biomedical subjects

J C Fruchart

Publications and source records attributed to J C Fruchart.

At least 523 records · Page 29Linked to original sources
PubMedDate not supplied

The effects of fibrates and thiazolidinediones on plasma triglyceride metabolism are mediated by distinct peroxisome proliferator activated receptors (PPARs).

The hypolipidemic fibrates and antidiabetic thiazolidinediones display potent triglyceride-lowering activities. Studies on the molecular action mechanisms of these compounds indicate that thiazolidinediones and fibrates exert their action by activating distinct transcription factors of the peroxisome proliferator activated receptor (PPAR) family, resulting in increased expression of lipoprotein lipase (LPL) and decreased expression of apolipoprotein (apo) C-III, both key-players in plasma triglyceride metabolism. Fibrates, on the one hand, are PPAR alpha activators, which selectively induce LPL mRNA levels and activity in the liver. Furthermore, hepatic apo C-III mRNA levels and protein production strongly decrease after fibrate treatment. On the other hand, thiazolidinediones, which are high affinity ligands for PPAR gamma, have no effect in the liver, but act primarily on adipose tissue, where they induce LPL mRNA levels and activity. The modulation of the expression of the LPL and apo C-III genes in liver and adipose tissue is correlated with the tissue-specific distribution of the respective PPARs (PPAR gamma expression being restricted to adipose tissue, whereas PPAR alpha is expressed predominantly in liver) confirming that fibrates and thiazolidinediones exert their effects primarily through PPAR alpha and PPAR gamma respectively. This distinct tissue-specific transcriptional regulation of genes involved in lipid metabolism by fibrates and thiazolidinediones indicates that research of compounds displaying combined PPAR alpha and PPAR gamma activation potential should lead to the discovery of more potent triglyceride-lowering drugs, which may be of use in the treatment of hypertriglyceridemia.

Adipose Tissue↗
PubMedDate not supplied

Interaction of LpB, LpB:E, LpB:C-III, and LpB:C-III:E lipoproteins with the low density lipoprotein receptor of HeLa cells.

In this study we measured the binding parameters of different apolipoprotein (apo) B-containing lipoproteins to the low density lipoprotein (LDL) receptor of HeLa cells. Our goal was to determine the respective roles of the different apolipoproteins of these particles, with particular emphasis on apos B, E, and C-III. Very low density lipoprotein from hypertriglyceridemic subjects (B to E molar ratio = 1:16) bound to HeLa cells with an affinity higher than that of LDL, but the apparent number of binding sites per cell was lower. Because of the heterogeneity of these lipoproteins, which were isolated by ultracentrifugation, we used immunoaffinity chromatography to define these particles on the basis of their apolipoprotein content. Lipoprotein B (LpB) particles that contained apo B as their sole apolipoprotein had lower affinity for the LDL receptor than did total LDL but had an apparently higher number of binding sites. The presence of apo E of phenotype E3/E3 or E4/E4 on one particle increased the affinity of the apo B-containing lipoprotein for the LDL receptor. The apparent number of binding sites decreased, probably due to the fact that a lipoprotein particle containing multiple copies of apo E bound to more than one molecule of LDL receptor. Interaction with several LDL receptors would also explain the higher binding affinity that we observed. The calculated number of binding sites expressed for each apo E molecule is close to the number of binding sites for lipoproteins containing only apo B (LpB or LDL), indicating that each apo E can interact with one LDL receptor. When the apo E phenotype was E2/E2, the LpB:E lipoproteins did not bind to the LDL receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Somatic gene transfer of human ApoA-I inhibits atherosclerosis progression in mouse models.

BACKGROUND: Apolipoprotein (apo) A-I is the major component of HDL, and it displays antiatherogenic properties. METHODS AND RESULTS: The human apoA-I gene has been transferred into different mouse models by use of a recombinant adenovirus under the control of an RSV-LTR promoter (AV RSV apoA-I). Administration of AV RSV apoA-I to C57BL/6 mice resulted in moderate expression of human apoA-I for 3 weeks, leading to a transient elevation (40% at day 11 after injection) of HDL cholesterol concentration. In contrast, administration of AV RSV apoA-I to human apoA-I-transgenic mice induced a large increase of human apoA-I and HDL cholesterol concentrations (300% and 360%, respectively, at day 14 after injection) for 10 weeks, indicating that an immune response to the transgene was one major hurdle for long-term duration of expression. Recombinant adenovirus expressing human apolipoprotein A-I (AV RSV apoA-I) was also injected into human apoA-I-transgenic/apoE-deficient mice, which are prone to develop atherosclerosis. Over a 6-week period, overexpression of human apoA-I inhibited fatty streak lesion formation by 56% in comparison with control. CONCLUSIONS: Somatic gene transfer of human apoA-I prevents the development of atherosclerosis in the mouse model.

Adenoviridae↗
PubMedDate not supplied

[Mechanism of action of hypolipemic drugs].

Hypolipemic drugs decrease the plasmatic concentrations of atherogenic lipoproteins, especially LDL. Two main drug families are used: fibrates and inhibitors of HMG CoA reductase. Fibrates act essentially as an activator of lipoprotein lipase and by increasing the catabolism of triglyceride rich lipoproteins. Further, they have a slight and non specific inhibitory effect on HMG CoA reductase activity, while, the new drug family of "statines" have a high, specific inhibitory effect on this essential enzyme of the cholesterol synthesis pathway. This enzymatic inhibition decreases the cholesterol synthesis and increases the activity of the hepatic LDL receptors, which are in charge of LDL elimination from the body. Resins entrap biliary salts and increase the cholesterol loss in feces and induce an over expression of the LDL receptors of the hepatocytes. Probucol inhibits atherogenesis by decreasing both LDL and HDL cholesterol and delaying LDL oxidative processing which is now believed to be one of the major factors of atherogenicity.

Cholesterol↗
PubMedDate not supplied

Serum amyloid A concentrations in giant-cell arteritis and polymyalgia rheumatica: a useful test in the management of the disease.

A prospective clinical study of 23 patients with giant-cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) was undertaken in order to assess the behaviour of the non-specific markers of the disease activity, the erythrocyte sedimentation rate (ESR) and other acute phase markers, particularly the C-reactive protein (CPR) and serum amyloid A apolipoprotein (apo SAA) levels during induction of disease remission by prednisone therapy, and possible further recurrence of GCA and/or PMR. The apo SAA measurement is more sensitive than the CRP measurement in determining disease activity (97% and 61%, respectively). The specificity of apo SAA is greater than ESR in the determination of inactive disease (86% and 77%, respectively). In some cases with clinically active disease the ESR and CRP were normal, whereas the apo SAA was always elevated. We conclude that the apo SAA measurement in combination with clinical data and other laboratory parameters may be useful in the management of GCA and/or PMR.

Acute-Phase Proteins↗
PubMedDate not supplied

Depletion in choline containing phospholipids of LpB particles in adequately controlled type I insulin-dependent diabetes mellitus.

The aim of the present study was to evaluate the serum and lipoprotein levels of choline--containing phospholipids (lecithin, lysolecithin and sphingomyelin) in a group of type I diabetic patients in fair metabolic control. Forty-eight male adult diabetic patients without macroproteinuria were compared with 48 healthy controls matched for age and body weight. Total cholesterol and phospholipids were assessed in plasma and in apolipoprotein B (apoB) and non apoB containing lipoprotein particles (Lp B and Lp non B particles) separated using precipitation with Concanavalin A. When compared to the control group, diabetic patients have significantly lower serum phospholipids and phospholipids and cholesterol content of LpB particles. All the other parameters studied were similar in the two groups. The phospholipids/cholesterol ratio, calculated in LpB particles is also significantly reduced in the diabetic group. These results strongly suggest a depletion in the choline containing phospholipid content of LpB particles and therefore an alteration of the surface components of atherogenic particles in type I diabetes mellitus.

Adult↗
PubMedDate not supplied

[Methods for studying the metabolism of lipoproteins].

The present diagnosis and control of dyslipoproteinemia require the analysis, not only of lipids, but also that of their carriers, the lipoproteins, as well as that of the enzymes necessary to their metabolism. Qualitative and quantitative techniques of analysis of lipoproteins have been described. Apolipoprotein quantitation methods have been brought to memory, calling attention to the specific problems related with these determinations, particularly in the case of immunological techniques. The clinical interest of these evaluations has been discussed and the various corresponding pathologies have been mentioned briefly.

Animals↗
PubMedDate not supplied

Lack of relationship between Lp(a) particle levels and albumin excretion rate in type 1 diabetic patients.

The excess risk of cardiovascular disease in Type 1 diabetes mellitus compared to non diabetic subjects is only partially explained by standard risk factors. Several studies suggest that Lp(a) concentrations are increased in Type 1 diabetes mellitus, but data are still controversial. Moreover, a high cardiovascular risk has been reported in diabetic patients with persistent proteinuria. Therefore, the aim of this study was to compare the Lp(a) particle levels in insulin-dependent diabetic patients with or without increased urinary albumin excretion. Cross-sectional study of Lp(a) plasma levels in a population of 140 insulin-dependent diabetic patients: 83 without increased proteinuria, 14 with borderline elevation of urinary albumin excretion, 27 with micro- and 16 with macro-proteinuria. Simultaneous determination of plasma lipids, fasting blood glucose and HbA1c was performed. The mean plasma Lp(a) concentrations and the distribution of the levels were comparable in all of the diabetic patient groups. No relationship existed between Lp(a) and HbA1c, fasting blood glucose or any lipid plasma levels. No influence of albumin excretion rate on Lp(a) levels was observed. These data provide no evidence of a specific contribution of Lp(a) particles to the increased morbidity and mortality from cardiovascular disease observed among patients with nephropathy.

Adult↗